Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Parkin- and PINK1-Dependent Mitophagy in Neurons: Will the Real Pathway Please Stand Up?</title><author><name sortKey="Grenier, Karl" sort="Grenier, Karl" uniqKey="Grenier K" first="Karl" last="Grenier">Karl Grenier</name><affiliation><nlm:aff id="aff1"><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Mclelland, Gian Luca" sort="Mclelland, Gian Luca" uniqKey="Mclelland G" first="Gian-Luca" last="Mclelland">Gian-Luca Mclelland</name><affiliation><nlm:aff id="aff1"><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Fon, Edward A" sort="Fon, Edward A" uniqKey="Fon E" first="Edward A." last="Fon">Edward A. Fon</name><affiliation><nlm:aff id="aff1"><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23882257</idno><idno type="pmc">3715719</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715719</idno><idno type="RBID">PMC:3715719</idno><idno type="doi">10.3389/fneur.2013.00100</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000C27</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C27</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Parkin- and PINK1-Dependent Mitophagy in Neurons: Will the Real Pathway Please Stand Up?</title><author><name sortKey="Grenier, Karl" sort="Grenier, Karl" uniqKey="Grenier K" first="Karl" last="Grenier">Karl Grenier</name><affiliation><nlm:aff id="aff1"><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Mclelland, Gian Luca" sort="Mclelland, Gian Luca" uniqKey="Mclelland G" first="Gian-Luca" last="Mclelland">Gian-Luca Mclelland</name><affiliation><nlm:aff id="aff1"><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Fon, Edward A" sort="Fon, Edward A" uniqKey="Fon E" first="Edward A." last="Fon">Edward A. Fon</name><affiliation><nlm:aff id="aff1"><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></nlm:aff></affiliation></author></analytic><series><title level="j">Frontiers in Neurology</title><idno type="eISSN">1664-2295</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson’s disease (PD) is characterized by massive degeneration of dopaminergic neurons in the <italic>substantia nigra</italic>. Whereas the majority of PD cases are sporadic, about 5–10% of cases are familial and associated with genetic factors. The loss of parkin or PINK1, two such factors, leads to an early onset form of PD. Importantly, recent studies have shown that parkin functions downstream of PINK1 in a common genetic pathway affecting mitochondrial homeostasis. More precisely, parkin has been shown to mediate the autophagy of damaged mitochondria (mitophagy) in a PINK1-dependent manner. However, much of the work characterizing this pathway has been carried out in immortalized cell lines overexpressing high levels of parkin. In contrast, whether or how endogenous parkin and PINK1 contribute to mitophagy in neurons is much less clear. Here we review recent work addressing the role of parkin/PINK1-dependent mitophagy in neurons. Clearly, it appears that mitophagy pathways differ spatially and kinetically in neurons and immortalized cells, and therefore might diverge in their ultimate outcome and function. While evidence suggests that parkin can translocate to mitochondria in neurons, the function and mechanism of mitophagy downstream of parkin recruitment in neurons remains to be clarified. Moreover, it is noteworthy that most work has focused on the downstream signaling events in parkin/PINK1 mitophagy, whereas the upstream signaling pathways remain comparatively poorly characterized. Identifying the upstream signaling mechanisms that trigger parkin/PINK1 mitophagy will help to explain the nature of the insults affecting mitochondrial function in PD, and a better understanding of these pathways in neurons will be the key in identifying new therapeutic targets in PD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lill, Cm" uniqKey="Lill C">CM Lill</name></author><author><name sortKey="Bertram, L" uniqKey="Bertram L">L Bertram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karbowski, M" uniqKey="Karbowski M">M Karbowski</name></author><author><name sortKey="Neutzner, A" uniqKey="Neutzner A">A Neutzner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Langston, Jw" uniqKey="Langston J">JW Langston</name></author><author><name sortKey="Ballard, P" uniqKey="Ballard P">P Ballard</name></author><author><name sortKey="Tetrud, Jw" uniqKey="Tetrud J">JW Tetrud</name></author><author><name sortKey="Irwin, I" uniqKey="Irwin I">I Irwin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schapira, Ah" uniqKey="Schapira A">AH Schapira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mann, Vm" uniqKey="Mann V">VM Mann</name></author><author><name sortKey="Cooper, Jm" uniqKey="Cooper J">JM Cooper</name></author><author><name sortKey="Krige, D" uniqKey="Krige D">D Krige</name></author><author><name sortKey="Daniel, Se" uniqKey="Daniel S">SE Daniel</name></author><author><name sortKey="Schapira, Ah" uniqKey="Schapira A">AH Schapira</name></author><author><name sortKey="Marsden, Cd" uniqKey="Marsden C">CD Marsden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bender, A" uniqKey="Bender A">A Bender</name></author><author><name sortKey="Krishnan, Kj" uniqKey="Krishnan K">KJ Krishnan</name></author><author><name sortKey="Morris, Cm" uniqKey="Morris C">CM Morris</name></author><author><name sortKey="Taylor, Ga" uniqKey="Taylor G">GA Taylor</name></author><author><name sortKey="Reeve, Ak" uniqKey="Reeve A">AK Reeve</name></author><author><name sortKey="Perry, Rh" uniqKey="Perry R">RH Perry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kraytsberg, Y" uniqKey="Kraytsberg Y">Y Kraytsberg</name></author><author><name sortKey="Kudryavtseva, E" uniqKey="Kudryavtseva E">E Kudryavtseva</name></author><author><name sortKey="Mckee, Ac" uniqKey="Mckee A">AC McKee</name></author><author><name sortKey="Geula, C" uniqKey="Geula C">C Geula</name></author><author><name sortKey="Kowall, Nw" uniqKey="Kowall N">NW Kowall</name></author><author><name sortKey="Khrapko, K" uniqKey="Khrapko K">K Khrapko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nunnari, J" uniqKey="Nunnari J">J Nunnari</name></author><author><name sortKey="Suomalainen, A" uniqKey="Suomalainen A">A Suomalainen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Westermann, B" uniqKey="Westermann B">B Westermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tatsuta, T" uniqKey="Tatsuta T">T Tatsuta</name></author><author><name sortKey="Langer, T" uniqKey="Langer T">T Langer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ashrafi, G" uniqKey="Ashrafi G">G Ashrafi</name></author><author><name sortKey="Schwarz, Tl" uniqKey="Schwarz T">TL Schwarz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shutt, Te" uniqKey="Shutt T">TE Shutt</name></author><author><name sortKey="Mcbride, Hm" uniqKey="Mcbride H">HM McBride</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soubannier, V" uniqKey="Soubannier V">V Soubannier</name></author><author><name sortKey="Mclelland, Gl" uniqKey="Mclelland G">GL McLelland</name></author><author><name sortKey="Zunino, R" uniqKey="Zunino R">R Zunino</name></author><author><name sortKey="Braschi, E" uniqKey="Braschi E">E Braschi</name></author><author><name sortKey="Rippstein, P" uniqKey="Rippstein P">P Rippstein</name></author><author><name sortKey="Fon, Ea" uniqKey="Fon E">EA Fon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soubannier, V" uniqKey="Soubannier V">V Soubannier</name></author><author><name sortKey="Rippstein, P" uniqKey="Rippstein P">P Rippstein</name></author><author><name sortKey="Kaufman, Ba" uniqKey="Kaufman B">BA Kaufman</name></author><author><name sortKey="Shoubridge, Ea" uniqKey="Shoubridge E">EA Shoubridge</name></author><author><name sortKey="Mcbride, Hm" uniqKey="Mcbride H">HM McBride</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Cs" uniqKey="Chan C">CS Chan</name></author><author><name sortKey="Gertler, Ts" uniqKey="Gertler T">TS Gertler</name></author><author><name sortKey="Surmeier, Dj" uniqKey="Surmeier D">DJ Surmeier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baxter, Rv" uniqKey="Baxter R">RV Baxter</name></author><author><name sortKey="Ben Othmane, K" uniqKey="Ben Othmane K">K Ben Othmane</name></author><author><name sortKey="Rochelle, Jm" uniqKey="Rochelle J">JM Rochelle</name></author><author><name sortKey="Stajich, Je" uniqKey="Stajich J">JE Stajich</name></author><author><name sortKey="Hulette, C" uniqKey="Hulette C">C Hulette</name></author><author><name sortKey="Dew Knight, S" uniqKey="Dew Knight S">S Dew-Knight</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cuesta, A" uniqKey="Cuesta A">A Cuesta</name></author><author><name sortKey="Pedrola, L" uniqKey="Pedrola L">L Pedrola</name></author><author><name sortKey="Sevilla, T" uniqKey="Sevilla T">T Sevilla</name></author><author><name sortKey="Garcia Planells, J" uniqKey="Garcia Planells J">J Garcia-Planells</name></author><author><name sortKey="Chumillas, Mj" uniqKey="Chumillas M">MJ Chumillas</name></author><author><name sortKey="Mayordomo, F" uniqKey="Mayordomo F">F Mayordomo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delettre, C" uniqKey="Delettre C">C Delettre</name></author><author><name sortKey="Lenaers, G" uniqKey="Lenaers G">G Lenaers</name></author><author><name sortKey="Griffoin, Jm" uniqKey="Griffoin J">JM Griffoin</name></author><author><name sortKey="Gigarel, N" uniqKey="Gigarel N">N Gigarel</name></author><author><name sortKey="Lorenzo, C" uniqKey="Lorenzo C">C Lorenzo</name></author><author><name sortKey="Belenguer, P" uniqKey="Belenguer P">P Belenguer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Di Bella, D" uniqKey="Di Bella D">D Di Bella</name></author><author><name sortKey="Lazzaro, F" uniqKey="Lazzaro F">F Lazzaro</name></author><author><name sortKey="Brusco, A" uniqKey="Brusco A">A Brusco</name></author><author><name sortKey="Plumari, M" uniqKey="Plumari M">M Plumari</name></author><author><name sortKey="Battaglia, G" uniqKey="Battaglia G">G Battaglia</name></author><author><name sortKey="Pastore, A" uniqKey="Pastore A">A Pastore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Edener, U" uniqKey="Edener U">U Edener</name></author><author><name sortKey="Wollner, J" uniqKey="Wollner J">J Wollner</name></author><author><name sortKey="Hehr, U" uniqKey="Hehr U">U Hehr</name></author><author><name sortKey="Kohl, Z" uniqKey="Kohl Z">Z Kohl</name></author><author><name sortKey="Schilling, S" uniqKey="Schilling S">S Schilling</name></author><author><name sortKey="Kreuz, F" uniqKey="Kreuz F">F Kreuz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shimura, H" uniqKey="Shimura H">H Shimura</name></author><author><name sortKey="Hattori, N" uniqKey="Hattori N">N Hattori</name></author><author><name sortKey="Kubo, S" uniqKey="Kubo S">S Kubo</name></author><author><name sortKey="Mizuno, Y" uniqKey="Mizuno Y">Y Mizuno</name></author><author><name sortKey="Asakawa, S" uniqKey="Asakawa S">S Asakawa</name></author><author><name sortKey="Minoshima, S" uniqKey="Minoshima S">S Minoshima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Valente, Em" uniqKey="Valente E">EM Valente</name></author><author><name sortKey="Abou Sleiman, Pm" uniqKey="Abou Sleiman P">PM Abou-Sleiman</name></author><author><name sortKey="Caputo, V" uniqKey="Caputo V">V Caputo</name></author><author><name sortKey="Muqit, Mm" uniqKey="Muqit M">MM Muqit</name></author><author><name sortKey="Harvey, K" uniqKey="Harvey K">K Harvey</name></author><author><name sortKey="Gispert, S" uniqKey="Gispert S">S Gispert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zuchner, S" uniqKey="Zuchner S">S Zuchner</name></author><author><name sortKey="Mersiyanova, Iv" uniqKey="Mersiyanova I">IV Mersiyanova</name></author><author><name sortKey="Muglia, M" uniqKey="Muglia M">M Muglia</name></author><author><name sortKey="Bissar Tadmouri, N" uniqKey="Bissar Tadmouri N">N Bissar-Tadmouri</name></author><author><name sortKey="Rochelle, J" uniqKey="Rochelle J">J Rochelle</name></author><author><name sortKey="Dadali, El" uniqKey="Dadali E">EL Dadali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schon, Ea" uniqKey="Schon E">EA Schon</name></author><author><name sortKey="Przedborski, S" uniqKey="Przedborski S">S Przedborski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, H" uniqKey="Deng H">H Deng</name></author><author><name sortKey="Dodson, Mw" uniqKey="Dodson M">MW Dodson</name></author><author><name sortKey="Huang, H" uniqKey="Huang H">H Huang</name></author><author><name sortKey="Guo, M" uniqKey="Guo M">M Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poole, Ac" uniqKey="Poole A">AC Poole</name></author><author><name sortKey="Thomas, Re" uniqKey="Thomas R">RE Thomas</name></author><author><name sortKey="Andrews, La" uniqKey="Andrews L">LA Andrews</name></author><author><name sortKey="Mcbride, Hm" uniqKey="Mcbride H">HM McBride</name></author><author><name sortKey="Whitworth, Aj" uniqKey="Whitworth A">AJ Whitworth</name></author><author><name sortKey="Pallanck, Lj" uniqKey="Pallanck L">LJ Pallanck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Exner, N" uniqKey="Exner N">N Exner</name></author><author><name sortKey="Treske, B" uniqKey="Treske B">B Treske</name></author><author><name sortKey="Paquet, D" uniqKey="Paquet D">D Paquet</name></author><author><name sortKey="Holmstrom, K" uniqKey="Holmstrom K">K Holmstrom</name></author><author><name sortKey="Schiesling, C" uniqKey="Schiesling C">C Schiesling</name></author><author><name sortKey="Gispert, S" uniqKey="Gispert S">S Gispert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lutz, Ak" uniqKey="Lutz A">AK Lutz</name></author><author><name sortKey="Exner, N" uniqKey="Exner N">N Exner</name></author><author><name sortKey="Fett, Me" uniqKey="Fett M">ME Fett</name></author><author><name sortKey="Schlehe, Js" uniqKey="Schlehe J">JS Schlehe</name></author><author><name sortKey="Kloos, K" uniqKey="Kloos K">K Kloos</name></author><author><name sortKey="Lammermann, K" uniqKey="Lammermann K">K Lammermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mortiboys, H" uniqKey="Mortiboys H">H Mortiboys</name></author><author><name sortKey="Thomas, Kj" uniqKey="Thomas K">KJ Thomas</name></author><author><name sortKey="Koopman, Wj" uniqKey="Koopman W">WJ Koopman</name></author><author><name sortKey="Klaffke, S" uniqKey="Klaffke S">S Klaffke</name></author><author><name sortKey="Abou Sleiman, P" uniqKey="Abou Sleiman P">P Abou-Sleiman</name></author><author><name sortKey="Olpin, S" uniqKey="Olpin S">S Olpin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amo, T" uniqKey="Amo T">T Amo</name></author><author><name sortKey="Sato, S" uniqKey="Sato S">S Sato</name></author><author><name sortKey="Saiki, S" uniqKey="Saiki S">S Saiki</name></author><author><name sortKey="Wolf, Am" uniqKey="Wolf A">AM Wolf</name></author><author><name sortKey="Toyomizu, M" uniqKey="Toyomizu M">M Toyomizu</name></author><author><name sortKey="Gautier, Ca" uniqKey="Gautier C">CA Gautier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gautier, Ca" uniqKey="Gautier C">CA Gautier</name></author><author><name sortKey="Kitada, T" uniqKey="Kitada T">T Kitada</name></author><author><name sortKey="Shen, J" uniqKey="Shen J">J Shen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gegg, Me" uniqKey="Gegg M">ME Gegg</name></author><author><name sortKey="Cooper, Jm" uniqKey="Cooper J">JM Cooper</name></author><author><name sortKey="Schapira, Ah" uniqKey="Schapira A">AH Schapira</name></author><author><name sortKey="Taanman, Jw" uniqKey="Taanman J">JW Taanman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morais, Va" uniqKey="Morais V">VA Morais</name></author><author><name sortKey="Verstreken, P" uniqKey="Verstreken P">P Verstreken</name></author><author><name sortKey="Roethig, A" uniqKey="Roethig A">A Roethig</name></author><author><name sortKey="Smet, J" uniqKey="Smet J">J Smet</name></author><author><name sortKey="Snellinx, A" uniqKey="Snellinx A">A Snellinx</name></author><author><name sortKey="Vanbrabant, M" uniqKey="Vanbrabant M">M Vanbrabant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vilain, S" uniqKey="Vilain S">S Vilain</name></author><author><name sortKey="Esposito, G" uniqKey="Esposito G">G Esposito</name></author><author><name sortKey="Haddad, D" uniqKey="Haddad D">D Haddad</name></author><author><name sortKey="Schaap, O" uniqKey="Schaap O">O Schaap</name></author><author><name sortKey="Dobreva, Mp" uniqKey="Dobreva M">MP Dobreva</name></author><author><name sortKey="Vos, M" uniqKey="Vos M">M Vos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gandhi, S" uniqKey="Gandhi S">S Gandhi</name></author><author><name sortKey="Wood Kaczmar, A" uniqKey="Wood Kaczmar A">A Wood-Kaczmar</name></author><author><name sortKey="Yao, Z" uniqKey="Yao Z">Z Yao</name></author><author><name sortKey="Plun Favreau, H" uniqKey="Plun Favreau H">H Plun-Favreau</name></author><author><name sortKey="Deas, E" uniqKey="Deas E">E Deas</name></author><author><name sortKey="Klupsch, K" uniqKey="Klupsch K">K Klupsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heeman, B" uniqKey="Heeman B">B Heeman</name></author><author><name sortKey="Van Den Haute, C" uniqKey="Van Den Haute C">C Van den Haute</name></author><author><name sortKey="Aelvoet, Sa" uniqKey="Aelvoet S">SA Aelvoet</name></author><author><name sortKey="Valsecchi, F" uniqKey="Valsecchi F">F Valsecchi</name></author><author><name sortKey="Rodenburg, Rj" uniqKey="Rodenburg R">RJ Rodenburg</name></author><author><name sortKey="Reumers, V" uniqKey="Reumers V">V Reumers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marongiu, R" uniqKey="Marongiu R">R Marongiu</name></author><author><name sortKey="Spencer, B" uniqKey="Spencer B">B Spencer</name></author><author><name sortKey="Crews, L" uniqKey="Crews L">L Crews</name></author><author><name sortKey="Adame, A" uniqKey="Adame A">A Adame</name></author><author><name sortKey="Patrick, C" uniqKey="Patrick C">C Patrick</name></author><author><name sortKey="Trejo, M" uniqKey="Trejo M">M Trejo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sandebring, A" uniqKey="Sandebring A">A Sandebring</name></author><author><name sortKey="Thomas, Kj" uniqKey="Thomas K">KJ Thomas</name></author><author><name sortKey="Beilina, A" uniqKey="Beilina A">A Beilina</name></author><author><name sortKey="Van Der Brug, M" uniqKey="Van Der Brug M">M van der Brug</name></author><author><name sortKey="Cleland, Mm" uniqKey="Cleland M">MM Cleland</name></author><author><name sortKey="Ahmad, R" uniqKey="Ahmad R">R Ahmad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greene, Aw" uniqKey="Greene A">AW Greene</name></author><author><name sortKey="Grenier, K" uniqKey="Grenier K">K Grenier</name></author><author><name sortKey="Aguileta, Ma" uniqKey="Aguileta M">MA Aguileta</name></author><author><name sortKey="Muise, S" uniqKey="Muise S">S Muise</name></author><author><name sortKey="Farazifard, R" uniqKey="Farazifard R">R Farazifard</name></author><author><name sortKey="Haque, Me" uniqKey="Haque M">ME Haque</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Sm" uniqKey="Jin S">SM Jin</name></author><author><name sortKey="Lazarou, M" uniqKey="Lazarou M">M Lazarou</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C Wang</name></author><author><name sortKey="Kane, La" uniqKey="Kane L">LA Kane</name></author><author><name sortKey="Narendra, Dp" uniqKey="Narendra D">DP Narendra</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lazarou, M" uniqKey="Lazarou M">M Lazarou</name></author><author><name sortKey="Jin, Sm" uniqKey="Jin S">SM Jin</name></author><author><name sortKey="Kane, La" uniqKey="Kane L">LA Kane</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narendra, Dp" uniqKey="Narendra D">DP Narendra</name></author><author><name sortKey="Jin, Sm" uniqKey="Jin S">SM Jin</name></author><author><name sortKey="Tanaka, A" uniqKey="Tanaka A">A Tanaka</name></author><author><name sortKey="Suen, Df" uniqKey="Suen D">DF Suen</name></author><author><name sortKey="Gautier, Ca" uniqKey="Gautier C">CA Gautier</name></author><author><name sortKey="Shen, J" uniqKey="Shen J">J Shen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geisler, S" uniqKey="Geisler S">S Geisler</name></author><author><name sortKey="Holmstrom, Km" uniqKey="Holmstrom K">KM Holmstrom</name></author><author><name sortKey="Skujat, D" uniqKey="Skujat D">D Skujat</name></author><author><name sortKey="Fiesel, Fc" uniqKey="Fiesel F">FC Fiesel</name></author><author><name sortKey="Rothfuss, Oc" uniqKey="Rothfuss O">OC Rothfuss</name></author><author><name sortKey="Kahle, Pj" uniqKey="Kahle P">PJ Kahle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lazarou, M" uniqKey="Lazarou M">M Lazarou</name></author><author><name sortKey="Narendra, Dp" uniqKey="Narendra D">DP Narendra</name></author><author><name sortKey="Jin, Sm" uniqKey="Jin S">SM Jin</name></author><author><name sortKey="Tekle, E" uniqKey="Tekle E">E Tekle</name></author><author><name sortKey="Banerjee, S" uniqKey="Banerjee S">S Banerjee</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsuda, N" uniqKey="Matsuda N">N Matsuda</name></author><author><name sortKey="Sato, S" uniqKey="Sato S">S Sato</name></author><author><name sortKey="Shiba, K" uniqKey="Shiba K">K Shiba</name></author><author><name sortKey="Okatsu, K" uniqKey="Okatsu K">K Okatsu</name></author><author><name sortKey="Saisho, K" uniqKey="Saisho K">K Saisho</name></author><author><name sortKey="Gautier, Ca" uniqKey="Gautier C">CA Gautier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shiba Fukushima, K" uniqKey="Shiba Fukushima K">K Shiba-Fukushima</name></author><author><name sortKey="Imai, Y" uniqKey="Imai Y">Y Imai</name></author><author><name sortKey="Yoshida, S" uniqKey="Yoshida S">S Yoshida</name></author><author><name sortKey="Ishihama, Y" uniqKey="Ishihama Y">Y Ishihama</name></author><author><name sortKey="Kanao, T" uniqKey="Kanao T">T Kanao</name></author><author><name sortKey="Sato, S" uniqKey="Sato S">S Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vives Bauza, C" uniqKey="Vives Bauza C">C Vives-Bauza</name></author><author><name sortKey="Zhou, C" uniqKey="Zhou C">C Zhou</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Cui, M" uniqKey="Cui M">M Cui</name></author><author><name sortKey="De Vries, Rl" uniqKey="De Vries R">RL de Vries</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Nc" uniqKey="Chan N">NC Chan</name></author><author><name sortKey="Salazar, Am" uniqKey="Salazar A">AM Salazar</name></author><author><name sortKey="Pham, Ah" uniqKey="Pham A">AH Pham</name></author><author><name sortKey="Sweredoski, Mj" uniqKey="Sweredoski M">MJ Sweredoski</name></author><author><name sortKey="Kolawa, Nj" uniqKey="Kolawa N">NJ Kolawa</name></author><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gegg, Me" uniqKey="Gegg M">ME Gegg</name></author><author><name sortKey="Cooper, Jm" uniqKey="Cooper J">JM Cooper</name></author><author><name sortKey="Chau, Ky" uniqKey="Chau K">KY Chau</name></author><author><name sortKey="Rojo, M" uniqKey="Rojo M">M Rojo</name></author><author><name sortKey="Schapira, Ah" uniqKey="Schapira A">AH Schapira</name></author><author><name sortKey="Taanman, Jw" uniqKey="Taanman J">JW Taanman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narendra, D" uniqKey="Narendra D">D Narendra</name></author><author><name sortKey="Tanaka, A" uniqKey="Tanaka A">A Tanaka</name></author><author><name sortKey="Suen, Df" uniqKey="Suen D">DF Suen</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poole, Ac" uniqKey="Poole A">AC Poole</name></author><author><name sortKey="Thomas, Re" uniqKey="Thomas R">RE Thomas</name></author><author><name sortKey="Yu, S" uniqKey="Yu S">S Yu</name></author><author><name sortKey="Vincow, Es" uniqKey="Vincow E">ES Vincow</name></author><author><name sortKey="Pallanck, L" uniqKey="Pallanck L">L Pallanck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, A" uniqKey="Tanaka A">A Tanaka</name></author><author><name sortKey="Cleland, Mm" uniqKey="Cleland M">MM Cleland</name></author><author><name sortKey="Xu, S" uniqKey="Xu S">S Xu</name></author><author><name sortKey="Narendra, Dp" uniqKey="Narendra D">DP Narendra</name></author><author><name sortKey="Suen, Df" uniqKey="Suen D">DF Suen</name></author><author><name sortKey="Karbowski, M" uniqKey="Karbowski M">M Karbowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Winter, D" uniqKey="Winter D">D Winter</name></author><author><name sortKey="Ashrafi, G" uniqKey="Ashrafi G">G Ashrafi</name></author><author><name sortKey="Schlehe, J" uniqKey="Schlehe J">J Schlehe</name></author><author><name sortKey="Wong, Yl" uniqKey="Wong Y">YL Wong</name></author><author><name sortKey="Selkoe, D" uniqKey="Selkoe D">D Selkoe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshii, Sr" uniqKey="Yoshii S">SR Yoshii</name></author><author><name sortKey="Kishi, C" uniqKey="Kishi C">C Kishi</name></author><author><name sortKey="Ishihara, N" uniqKey="Ishihara N">N Ishihara</name></author><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ziviani, E" uniqKey="Ziviani E">E Ziviani</name></author><author><name sortKey="Tao, Rn" uniqKey="Tao R">RN Tao</name></author><author><name sortKey="Whitworth, Aj" uniqKey="Whitworth A">AJ Whitworth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Ney, Pa" uniqKey="Ney P">PA Ney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narendra, D" uniqKey="Narendra D">D Narendra</name></author><author><name sortKey="Kane, La" uniqKey="Kane L">LA Kane</name></author><author><name sortKey="Hauser Dn, I" uniqKey="Hauser Dn I">I Hauser DN</name></author><author><name sortKey="Fearnley, M" uniqKey="Fearnley M">M Fearnley</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okatsu, K" uniqKey="Okatsu K">K Okatsu</name></author><author><name sortKey="Saisho, K" uniqKey="Saisho K">K Saisho</name></author><author><name sortKey="Shimanuki, M" uniqKey="Shimanuki M">M Shimanuki</name></author><author><name sortKey="Nakada, K" uniqKey="Nakada K">K Nakada</name></author><author><name sortKey="Shitara, H" uniqKey="Shitara H">H Shitara</name></author><author><name sortKey="Sou, Ys" uniqKey="Sou Y">YS Sou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suen, Df" uniqKey="Suen D">DF Suen</name></author><author><name sortKey="Narendra, Dp" uniqKey="Narendra D">DP Narendra</name></author><author><name sortKey="Tanaka, A" uniqKey="Tanaka A">A Tanaka</name></author><author><name sortKey="Manfredi, G" uniqKey="Manfredi G">G Manfredi</name></author><author><name sortKey="Youle, Rj" uniqKey="Youle R">RJ Youle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ney, Pa" uniqKey="Ney P">PA Ney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heynen, Mj" uniqKey="Heynen M">MJ Heynen</name></author><author><name sortKey="Verwilghen, Rl" uniqKey="Verwilghen R">RL Verwilghen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fader, Cm" uniqKey="Fader C">CM Fader</name></author><author><name sortKey="Colombo, Mi" uniqKey="Colombo M">MI Colombo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ding, Wx" uniqKey="Ding W">WX Ding</name></author><author><name sortKey="Ni, Hm" uniqKey="Ni H">HM Ni</name></author><author><name sortKey="Li, M" uniqKey="Li M">M Li</name></author><author><name sortKey="Liao, Y" uniqKey="Liao Y">Y Liao</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Stolz, Db" uniqKey="Stolz D">DB Stolz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Novak, I" uniqKey="Novak I">I Novak</name></author><author><name sortKey="Kirkin, V" uniqKey="Kirkin V">V Kirkin</name></author><author><name sortKey="Mcewan, Dg" uniqKey="Mcewan D">DG McEwan</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Wild, P" uniqKey="Wild P">P Wild</name></author><author><name sortKey="Rozenknop, A" uniqKey="Rozenknop A">A Rozenknop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Randall, Ms" uniqKey="Randall M">MS Randall</name></author><author><name sortKey="Loyd, Mr" uniqKey="Loyd M">MR Loyd</name></author><author><name sortKey="Dorsey, Fc" uniqKey="Dorsey F">FC Dorsey</name></author><author><name sortKey="Kundu, M" uniqKey="Kundu M">M Kundu</name></author><author><name sortKey="Cleveland, Jl" uniqKey="Cleveland J">JL Cleveland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sandoval, H" uniqKey="Sandoval H">H Sandoval</name></author><author><name sortKey="Thiagarajan, P" uniqKey="Thiagarajan P">P Thiagarajan</name></author><author><name sortKey="Dasgupta, Sk" uniqKey="Dasgupta S">SK Dasgupta</name></author><author><name sortKey="Schumacher, A" uniqKey="Schumacher A">A Schumacher</name></author><author><name sortKey="Prchal, Jt" uniqKey="Prchal J">JT Prchal</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schweers, Rl" uniqKey="Schweers R">RL Schweers</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Randall, Ms" uniqKey="Randall M">MS Randall</name></author><author><name sortKey="Loyd, Mr" uniqKey="Loyd M">MR Loyd</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Dorsey, Fc" uniqKey="Dorsey F">FC Dorsey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mortensen, M" uniqKey="Mortensen M">M Mortensen</name></author><author><name sortKey="Ferguson, Dj" uniqKey="Ferguson D">DJ Ferguson</name></author><author><name sortKey="Edelmann, M" uniqKey="Edelmann M">M Edelmann</name></author><author><name sortKey="Kessler, B" uniqKey="Kessler B">B Kessler</name></author><author><name sortKey="Morten, Kj" uniqKey="Morten K">KJ Morten</name></author><author><name sortKey="Komatsu, M" uniqKey="Komatsu M">M Komatsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dumollard, R" uniqKey="Dumollard R">R Dumollard</name></author><author><name sortKey="Duchen, M" uniqKey="Duchen M">M Duchen</name></author><author><name sortKey="Carroll, J" uniqKey="Carroll J">J Carroll</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Rawi, S" uniqKey="Al Rawi S">S Al Rawi</name></author><author><name sortKey="Louvet Vallee, S" uniqKey="Louvet Vallee S">S Louvet-Vallee</name></author><author><name sortKey="Djeddi, A" uniqKey="Djeddi A">A Djeddi</name></author><author><name sortKey="Sachse, M" uniqKey="Sachse M">M Sachse</name></author><author><name sortKey="Culetto, E" uniqKey="Culetto E">E Culetto</name></author><author><name sortKey="Hajjar, C" uniqKey="Hajjar C">C Hajjar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cummins, Jm" uniqKey="Cummins J">JM Cummins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sato, M" uniqKey="Sato M">M Sato</name></author><author><name sortKey="Sato, K" uniqKey="Sato K">K Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clark, Ie" uniqKey="Clark I">IE Clark</name></author><author><name sortKey="Dodson, Mw" uniqKey="Dodson M">MW Dodson</name></author><author><name sortKey="Jiang, C" uniqKey="Jiang C">C Jiang</name></author><author><name sortKey="Cao, Jh" uniqKey="Cao J">JH Cao</name></author><author><name sortKey="Huh, Jr" uniqKey="Huh J">JR Huh</name></author><author><name sortKey="Seol, Jh" uniqKey="Seol J">JH Seol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greene, Jc" uniqKey="Greene J">JC Greene</name></author><author><name sortKey="Whitworth, Aj" uniqKey="Whitworth A">AJ Whitworth</name></author><author><name sortKey="Kuo, I" uniqKey="Kuo I">I Kuo</name></author><author><name sortKey="Andrews, La" uniqKey="Andrews L">LA Andrews</name></author><author><name sortKey="Feany, Mb" uniqKey="Feany M">MB Feany</name></author><author><name sortKey="Pallanck, Lj" uniqKey="Pallanck L">LJ Pallanck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, J" uniqKey="Park J">J Park</name></author><author><name sortKey="Lee, Sb" uniqKey="Lee S">SB Lee</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S Lee</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name></author><author><name sortKey="Song, S" uniqKey="Song S">S Song</name></author><author><name sortKey="Kim, S" uniqKey="Kim S">S Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, Q" uniqKey="Cai Q">Q Cai</name></author><author><name sortKey="Zakaria, Hm" uniqKey="Zakaria H">HM Zakaria</name></author><author><name sortKey="Simone, A" uniqKey="Simone A">A Simone</name></author><author><name sortKey="Sheng, Zh" uniqKey="Sheng Z">ZH Sheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Joselin, Ap" uniqKey="Joselin A">AP Joselin</name></author><author><name sortKey="Hewitt, Sj" uniqKey="Hewitt S">SJ Hewitt</name></author><author><name sortKey="Callaghan, Sm" uniqKey="Callaghan S">SM Callaghan</name></author><author><name sortKey="Kim, Rh" uniqKey="Kim R">RH Kim</name></author><author><name sortKey="Chung, Yh" uniqKey="Chung Y">YH Chung</name></author><author><name sortKey="Mak, Tw" uniqKey="Mak T">TW Mak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seibler, P" uniqKey="Seibler P">P Seibler</name></author><author><name sortKey="Graziotto, J" uniqKey="Graziotto J">J Graziotto</name></author><author><name sortKey="Jeong, H" uniqKey="Jeong H">H Jeong</name></author><author><name sortKey="Simunovic, F" uniqKey="Simunovic F">F Simunovic</name></author><author><name sortKey="Klein, C" uniqKey="Klein C">C Klein</name></author><author><name sortKey="Krainc, D" uniqKey="Krainc D">D Krainc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Laar, Vs" uniqKey="Van Laar V">VS Van Laar</name></author><author><name sortKey="Arnold, B" uniqKey="Arnold B">B Arnold</name></author><author><name sortKey="Cassady, Sj" uniqKey="Cassady S">SJ Cassady</name></author><author><name sortKey="Chu, Ct" uniqKey="Chu C">CT Chu</name></author><author><name sortKey="Burton, Ea" uniqKey="Burton E">EA Burton</name></author><author><name sortKey="Berman, Sb" uniqKey="Berman S">SB Berman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rakovic, A" uniqKey="Rakovic A">A Rakovic</name></author><author><name sortKey="Shurkewitsch, K" uniqKey="Shurkewitsch K">K Shurkewitsch</name></author><author><name sortKey="Seibler, P" uniqKey="Seibler P">P Seibler</name></author><author><name sortKey="Grunewald, A" uniqKey="Grunewald A">A Grunewald</name></author><author><name sortKey="Zanon, A" uniqKey="Zanon A">A Zanon</name></author><author><name sortKey="Hagenah, J" uniqKey="Hagenah J">J Hagenah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almeida, A" uniqKey="Almeida A">A Almeida</name></author><author><name sortKey="Almeida, J" uniqKey="Almeida J">J Almeida</name></author><author><name sortKey="Bolanos, Jp" uniqKey="Bolanos J">JP Bolanos</name></author><author><name sortKey="Moncada, S" uniqKey="Moncada S">S Moncada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almeida, A" uniqKey="Almeida A">A Almeida</name></author><author><name sortKey="Moncada, S" uniqKey="Moncada S">S Moncada</name></author><author><name sortKey="Bolanos, Jp" uniqKey="Bolanos J">JP Bolanos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bolanos, Jp" uniqKey="Bolanos J">JP Bolanos</name></author><author><name sortKey="Almeida, A" uniqKey="Almeida A">A Almeida</name></author><author><name sortKey="Moncada, S" uniqKey="Moncada S">S Moncada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herrero Mendez, A" uniqKey="Herrero Mendez A">A Herrero-Mendez</name></author><author><name sortKey="Almeida, A" uniqKey="Almeida A">A Almeida</name></author><author><name sortKey="Fernandez, E" uniqKey="Fernandez E">E Fernandez</name></author><author><name sortKey="Maestre, C" uniqKey="Maestre C">C Maestre</name></author><author><name sortKey="Moncada, S" uniqKey="Moncada S">S Moncada</name></author><author><name sortKey="Bolanos, Jp" uniqKey="Bolanos J">JP Bolanos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekstrand, Mi" uniqKey="Ekstrand M">MI Ekstrand</name></author><author><name sortKey="Terzioglu, M" uniqKey="Terzioglu M">M Terzioglu</name></author><author><name sortKey="Galter, D" uniqKey="Galter D">D Galter</name></author><author><name sortKey="Zhu, S" uniqKey="Zhu S">S Zhu</name></author><author><name sortKey="Hofstetter, C" uniqKey="Hofstetter C">C Hofstetter</name></author><author><name sortKey="Lindqvist, E" uniqKey="Lindqvist E">E Lindqvist</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sterky, Fh" uniqKey="Sterky F">FH Sterky</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S Lee</name></author><author><name sortKey="Wibom, R" uniqKey="Wibom R">R Wibom</name></author><author><name sortKey="Olson, L" uniqKey="Olson L">L Olson</name></author><author><name sortKey="Larsson, Ng" uniqKey="Larsson N">NG Larsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vincow, Es" uniqKey="Vincow E">ES Vincow</name></author><author><name sortKey="Merrihew, G" uniqKey="Merrihew G">G Merrihew</name></author><author><name sortKey="Thomas, Re" uniqKey="Thomas R">RE Thomas</name></author><author><name sortKey="Shulman, Nj" uniqKey="Shulman N">NJ Shulman</name></author><author><name sortKey="Beyer, Rp" uniqKey="Beyer R">RP Beyer</name></author><author><name sortKey="Maccoss, Mj" uniqKey="Maccoss M">MJ Maccoss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Jy" uniqKey="Lee J">JY Lee</name></author><author><name sortKey="Nagano, Y" uniqKey="Nagano Y">Y Nagano</name></author><author><name sortKey="Taylor, Jp" uniqKey="Taylor J">JP Taylor</name></author><author><name sortKey="Lim, Kl" uniqKey="Lim K">KL Lim</name></author><author><name sortKey="Yao, Tp" uniqKey="Yao T">TP Yao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, Y" uniqKey="Sun Y">Y Sun</name></author><author><name sortKey="Vashisht, Aa" uniqKey="Vashisht A">AA Vashisht</name></author><author><name sortKey="Tchieu, J" uniqKey="Tchieu J">J Tchieu</name></author><author><name sortKey="Wohlschlegel, Ja" uniqKey="Wohlschlegel J">JA Wohlschlegel</name></author><author><name sortKey="Dreier, L" uniqKey="Dreier L">L Dreier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Humbeeck, C" uniqKey="Van Humbeeck C">C Van Humbeeck</name></author><author><name sortKey="Cornelissen, T" uniqKey="Cornelissen T">T Cornelissen</name></author><author><name sortKey="Hofkens, H" uniqKey="Hofkens H">H Hofkens</name></author><author><name sortKey="Mandemakers, W" uniqKey="Mandemakers W">W Mandemakers</name></author><author><name sortKey="Gevaert, K" uniqKey="Gevaert K">K Gevaert</name></author><author><name sortKey="De Strooper, B" uniqKey="De Strooper B">B De Strooper</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Neurol</journal-id><journal-id journal-id-type="iso-abbrev">Front Neurol</journal-id><journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id><journal-title-group><journal-title>Frontiers in Neurology</journal-title></journal-title-group><issn pub-type="epub">1664-2295</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23882257</article-id><article-id pub-id-type="pmc">3715719</article-id><article-id pub-id-type="doi">10.3389/fneur.2013.00100</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neuroscience</subject><subj-group><subject>Review Article</subject></subj-group></subj-group></article-categories><title-group><article-title>Parkin- and PINK1-Dependent Mitophagy in Neurons: Will the Real Pathway Please Stand Up?</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Grenier</surname><given-names>Karl</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>McLelland</surname><given-names>Gian-Luca</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fon</surname><given-names>Edward A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</institution>,<addr-line>Montreal, QC</addr-line>,<country>Canada</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Heather Lynn Montie, Philadelphia College of Osteopathic Medicine, USA</p></fn><fn fn-type="edited-by"><p>Reviewed by: Denis Soulet, Laval University, Canada; Kah-Leong Lim, National University of Singapore, Singapore</p></fn><corresp content-type="corresp" id="cor1">*Correspondence: Edward A. Fon, Montreal Neurological Institute, 3801 University Street, Montreal, QC H3A 2B4, Canada e-mail: <email>ted.fon@mcgill.ca</email></corresp><fn fn-type="other" id="fn001"><p>This article was submitted to Frontiers in Neurodegeneration, a specialty of Frontiers in Neurology.</p></fn></author-notes><pub-date pub-type="epreprint"><day>03</day><month>6</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>19</day><month>7</month><year>2013</year></pub-date><pub-date pub-type="collection"><year>2013</year></pub-date><volume>4</volume><elocation-id>100</elocation-id><history><date date-type="received"><day>31</day><month>3</month><year>2013</year></date><date date-type="accepted"><day>08</day><month>7</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Grenier, McLelland and Fon.</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.</license-p></license></permissions><abstract><p>Parkinson’s disease (PD) is characterized by massive degeneration of dopaminergic neurons in the <italic>substantia nigra</italic>. Whereas the majority of PD cases are sporadic, about 5–10% of cases are familial and associated with genetic factors. The loss of parkin or PINK1, two such factors, leads to an early onset form of PD. Importantly, recent studies have shown that parkin functions downstream of PINK1 in a common genetic pathway affecting mitochondrial homeostasis. More precisely, parkin has been shown to mediate the autophagy of damaged mitochondria (mitophagy) in a PINK1-dependent manner. However, much of the work characterizing this pathway has been carried out in immortalized cell lines overexpressing high levels of parkin. In contrast, whether or how endogenous parkin and PINK1 contribute to mitophagy in neurons is much less clear. Here we review recent work addressing the role of parkin/PINK1-dependent mitophagy in neurons. Clearly, it appears that mitophagy pathways differ spatially and kinetically in neurons and immortalized cells, and therefore might diverge in their ultimate outcome and function. While evidence suggests that parkin can translocate to mitochondria in neurons, the function and mechanism of mitophagy downstream of parkin recruitment in neurons remains to be clarified. Moreover, it is noteworthy that most work has focused on the downstream signaling events in parkin/PINK1 mitophagy, whereas the upstream signaling pathways remain comparatively poorly characterized. Identifying the upstream signaling mechanisms that trigger parkin/PINK1 mitophagy will help to explain the nature of the insults affecting mitochondrial function in PD, and a better understanding of these pathways in neurons will be the key in identifying new therapeutic targets in PD.</p></abstract><kwd-group><kwd>autophagy</kwd><kwd>Mitochondria</kwd><kwd>mitophagy</kwd><kwd>neurons</kwd><kwd>parkin</kwd><kwd>Parkinson’s disease</kwd><kwd>PINK1</kwd></kwd-group><counts><fig-count count="1"></fig-count><table-count count="3"></table-count><equation-count count="0"></equation-count><ref-count count="90"></ref-count><page-count count="8"></page-count><word-count count="6585"></word-count></counts></article-meta></front><body><sec id="S1"><title>Introduction</title><p>Over the past two decades, the identification of genes responsible for complex neurodegenerative disorders has profoundly changed our understanding of pathogenic mechanisms leading to neuronal cell death. Whereas previous research focused on post-mortem studies, analysis of the physiological function of causative genes now allows us to focus directly on key cellular pathways involved in pathology (<xref ref-type="bibr" rid="B1">1</xref>).</p><p>Among these pathways, dysregulation of mitochondrial quality control has emerged as a common theme for many neurological diseases and in particular for Parkinson’s disease (PD) (<xref ref-type="bibr" rid="B2">2</xref>). Mitochondrial dysfunction has been a longstanding theme in PD following observations that mitochondrial toxins such as MPTP and rotenone could induce acute parkinsonism (<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>) and that mitochondrial respiration was defective in the <italic>substantia nigra pars compacta</italic> (SNpc) of post-mortem PD patients (<xref ref-type="bibr" rid="B5">5</xref>). Furthermore, the SNpc of patient brains has been shown to have a higher occurrence of mtDNA deletions compared to aged-matched controls (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B7">7</xref>).</p><p>More recently, two PD-linked genes – parkin and PINK1 – have been implicated in mitochondrial quality control, via the degradation of dysfunctional mitochondria by autophagy (a process termed mitophagy). This suggests that the mitochondrial dysfunction observed in PD may be the result of compromised mitochondrial quality control mechanisms. Most studies examining this process, however, have employed immortalized cell lines in place of primary cell cultures, and few have studied it in neurons. In this review, we summarize the evidence for a physiological role for mitophagy in neurons, discussing the possible role of parkin and PINK1 in such a pathway and its relevance to PD.</p></sec><sec id="S2"><title>Mitochondrial Dynamics and Quality Control in Health and Disease</title><p>Mitochondria – double membrane-bound organelles originating from the symbiosis between an early eukaryotic cell and a prokaryotic cell – are essential for generating energy through the process of oxidative phosphorylation (OXPHOS) and also play important roles in fatty acid metabolism, apoptosis, and calcium-buffering (<xref ref-type="bibr" rid="B8">8</xref>).</p><p>Long regarded as individual, “bean-shaped” organelles, mitochondria are now understood as a dynamic, inter-connected network, linked to other organelles and important players in a myriad of cellular signaling pathways (<xref ref-type="bibr" rid="B9">9</xref>). By regulating the connectivity and the size of the mitochondrial network, the cell can regulate energy production and most other mitochondrial processes (<xref ref-type="bibr" rid="B9">9</xref>). While the shape of the mitochondrial network is controlled by fusion- and fission-specific GTPases, the size of the network is controlled by <italic>de novo</italic> mitochondrial biogenesis and macroautophagy.</p><p>Mitochondria are the cellular site of OXPHOS, as well as many other biosynthetic reactions. These essential processes generate, as by-products, reactive intermediates, and oxidizing agents, which in turn damage mitochondrial proteins and lipids (<xref ref-type="bibr" rid="B10">10</xref>). To this end, distinct mitochondrial quality control mechanisms – the degradation of unfolded mitochondrial proteins by mitochondrial proteases, the elimination of selective cargo by mitochondria-derived vesicles and the elimination of whole mitochondria by mitophagy – function in response to the degree of mitochondrial damage present (<xref ref-type="bibr" rid="B10">10</xref><xref ref-type="bibr" rid="B11"></xref><xref ref-type="bibr" rid="B12"></xref><xref ref-type="bibr" rid="B13"></xref>–<xref ref-type="bibr" rid="B14">14</xref>).</p><p>Nowhere is the requirement for effective mitochondrial quality control systems more important than in neurons, where high energetic demands and need for high calcium-buffering capacity due to action potential-driven calcium influxes rely heavily on proper mitochondrial function (<xref ref-type="bibr" rid="B15">15</xref>). This mitochondrial dependence renders neurons especially vulnerable to mitochondrial damage, and, in turn, efficient and properly functioning mitochondrial quality control pathways are paramount to neuronal survival. Highlighting this are genetic studies demonstrating the involvement of genes regulating mitochondrial morphology – MFN2 and GDAP-1 in Charcot-Marie-Tooth type2A, as well as OPA1in Optic Atrophy – and mitochondrial quality control – AFG3L2 in Spinocerebellar Ataxia type 28, parkin and PINK1 in PD – in neurodegenerative disease (<xref ref-type="bibr" rid="B16">16</xref><xref ref-type="bibr" rid="B17"></xref><xref ref-type="bibr" rid="B18"></xref><xref ref-type="bibr" rid="B19"></xref><xref ref-type="bibr" rid="B20"></xref><xref ref-type="bibr" rid="B21"></xref><xref ref-type="bibr" rid="B22"></xref>–<xref ref-type="bibr" rid="B23">23</xref>).</p></sec><sec id="S3"><title>The PINK1/Parkin Pathway: A Link between Mitochondrial Quality Control and Parkinson’s Disease</title><p>It has been hypothesized recently that the decline in mitochondrial function observed in PD may stem from the rapid deregulation of mitochondrial quality control mechanisms in patients affected by the disease (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B24">24</xref>). Importantly, recent studies have implicated two genes linked to autosomal-recessive juvenile parkinsonism (AR-JP) in humans – PINK1, a mitochondrially targeted serine/threonine kinase, and parkin, an E3 ubiquitin ligase – in a mitochondrial quality control pathway involving the degradation of damaged mitochondria by autophagy.</p><p>Initial genetic evidence from <italic>Drosophila</italic> had suggested that both parkin and PINK1 function in a common pathway regulating mitochondrial morphology by promoting mitochondrial fission – either by inhibiting the pro-fusion protein Fzo1 (the major <italic>Drosophila</italic> mitofusin homolog) or by activating the pro-fission protein Drp1 (<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B26">26</xref>). However, a clear consensus of how these genes affect morphology in mammalian cells has yet to be established (<xref ref-type="bibr" rid="B27">27</xref><xref ref-type="bibr" rid="B28"></xref>–<xref ref-type="bibr" rid="B29">29</xref>). In regulating mitochondrial function, however, PINK1 has been shown to promote mitochondrial respiration and increase mitochondrial membrane potential (Δψ<sub>m</sub>) (<xref ref-type="bibr" rid="B30">30</xref><xref ref-type="bibr" rid="B31"></xref>–<xref ref-type="bibr" rid="B32">32</xref>), with a specific link to complex I (<xref ref-type="bibr" rid="B33">33</xref>, <xref ref-type="bibr" rid="B34">34</xref>), as well as proper calcium homeostasis in mammalian cell lines (<xref ref-type="bibr" rid="B35">35</xref><xref ref-type="bibr" rid="B36"></xref><xref ref-type="bibr" rid="B37"></xref>–<xref ref-type="bibr" rid="B38">38</xref>).</p><p>Overwhelming evidence in mammalian cell lines has implicated parkin and PINK1 in the mitophagic degradation of dysfunctional, depolarized mitochondria. Upon ablation of Δψ<sub>m</sub> by the chemical uncoupler CCCP, the Δψ<sub>m</sub>-dependent mitochondrial import of PINK1 – a polypeptide that, basally, is rapidly turned over by proteases once inside mitochondria – is halted, allowing PINK1, bound to the TOM complex, to build up on the outer mitochondrial membrane (<xref ref-type="bibr" rid="B39">39</xref><xref ref-type="bibr" rid="B40"></xref><xref ref-type="bibr" rid="B41"></xref>–<xref ref-type="bibr" rid="B42">42</xref>). Here, PINK1 recruits parkin from the cytosol, in a manner dependent on functional PINK1 kinase activity, and promotes parkin’s E3 ubiquitin ligase activity, possibly through direct phosphorylation of parkin by PINK1 (<xref ref-type="bibr" rid="B43">43</xref><xref ref-type="bibr" rid="B44"></xref><xref ref-type="bibr" rid="B45"></xref><xref ref-type="bibr" rid="B46"></xref>–<xref ref-type="bibr" rid="B47">47</xref>). Once recruited to depolarized mitochondria, parkin-dependent ubiquitination and proteasomal degradation of outer membrane proteins – notably the mitofusins, VDACs, and Miro – ultimately lead to autophagy, a step that possibly involves the rupture of the outer mitochondrial membrane (<xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B48">48</xref><xref ref-type="bibr" rid="B49"></xref><xref ref-type="bibr" rid="B50"></xref><xref ref-type="bibr" rid="B51"></xref><xref ref-type="bibr" rid="B52"></xref><xref ref-type="bibr" rid="B53"></xref><xref ref-type="bibr" rid="B54"></xref>–<xref ref-type="bibr" rid="B55">55</xref>). PINK1-/parkin-dependent mitophagy enlists the canonical ATG (<italic>a</italic>u<italic>t</italic>opha<italic>g</italic>y-related gene) pathway, originally identified in yeast (<xref ref-type="bibr" rid="B56">56</xref>). The ubiquitination of mitochondrial proteins by parkin has been suggested to recruit ubiquitin-binding adaptor proteins, such as p62/SQSTM1, to depolarized mitochondria (<xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B57">57</xref>, <xref ref-type="bibr" rid="B58">58</xref>). This in turn was shown to induce mitochondrial clustering around the nucleus (<xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B57">57</xref>, <xref ref-type="bibr" rid="B58">58</xref>), possibly facilitating the autophagy of mitochondria by increasing their proximity to the endoplasmic reticulum, a possible source of autophagic membranes. Although PINK1/parkin mitophagy has not been fully characterized with respect to the canonical ATG pathway, the requirement for LC3, p62, and ATG5 suggests that depolarization-induced, PINK1-/parkin-dependent mitophagy indeed makes use of the conserved ATG pathway to remove damaged mitochondria.</p><p>Clearly, the ability to pharmacologically disrupt Δψ<sub>m</sub> has enabled the study of the PINK1/parkin pathway using a robust and effective paradigm, although parkin-dependent mitophagy has also been observed under less severe conditions. For example, in fusion-deficient cells, parkin recruitment to depolarized mitochondria (arising from uneven fission) has been demonstrated at the steady-state (<xref ref-type="bibr" rid="B50">50</xref>). Furthermore, in cells harboring severe mtDNA mutations, parkin has been shown to selectively remove dysfunctional mitochondria over time (<xref ref-type="bibr" rid="B59">59</xref>). However, a truly robust, physiological assay with which to determine the effectiveness of PINK1- and parkin-dependent mitophagy has remained elusive.</p></sec><sec id="S4"><title>Types of Mitophagy Under Physiological Conditions</title><p>Selective mitophagy (depicted in Figure <xref ref-type="fig" rid="F1">1</xref>) is critical during the development of cells that specifically degrade their mitochondria as they mature. The most-studied example concerns red blood cells (RBCs), which lose their mitochondria in order to transport oxygen instead of consuming it (<xref ref-type="bibr" rid="B60">60</xref>). While it was long known that RBCs are devoid of nuclei and organelles such as mitochondria and Golgi apparatus (<xref ref-type="bibr" rid="B61">61</xref>), only recently have studies identified mitophagy as the mechanism by which mitochondria are removed (<xref ref-type="bibr" rid="B62">62</xref>). Mitophagy in RBCs occurs canonically, according to the conserved ATG protein pathway (<xref ref-type="bibr" rid="B56">56</xref>), as well as through a redundant ATG7-independent mechanism involving NIX/BNIP3L, a protein related to Bcl-2 (<xref ref-type="bibr" rid="B63">63</xref><xref ref-type="bibr" rid="B64"></xref>–<xref ref-type="bibr" rid="B65">65</xref>). Moreover, NIX/BNIP3L has been shown to be an essential mediator of mitochondrial depolarization prior to autophagy (<xref ref-type="bibr" rid="B66">66</xref>, <xref ref-type="bibr" rid="B67">67</xref>).</p><fig id="F1" position="float"><label>Figure 1</label><caption><p><bold>Comparison of known mitophagy pathways (Reticulocytes, PINK1/Parkin, and Fertilized oocyte) in four major steps</bold>. (1) Upstream signaling or mitochondrial damage activates mitophagy pathways. (2) The initial mitochondrial signaling or mitochondrial damage converges at a flagship protein, which amplifies the signal. (3) Mitochondria are transported to isolation membrane-rich sites and marked for either proteasomal or autophagic degradation. (4) Mitochondria are enveloped by isolation membranes and delivered to autophagosomes. Δψ, mitochondrial membrane potential; LC3, microtubule-associated protein 1 light chain 3; LGG-1, LC3, GABARAP, and GATE16 family 1; Mfn2, mitofusin 2; mtDNA, mitochondrial DNA; NIX, NIP3-like protein X; PINK1, PTEN-induced putative kinase 1; Ub, ubiquitin; VDAC, voltage-dependent anion channel.</p></caption><graphic xlink:href="fneur-04-00100-g001"></graphic></fig><p>The observation that both NIX- and parkin-/PINK1-dependent mitophagy seem to rely on mitochondrial depolarization as an upstream mechanism prior to autophagy suggests a conserved mechanism among pathways (Table <xref ref-type="table" rid="T1">1</xref>), whether they are programed (reticulocyte differentiation) or reactionary (parkin/PINK1). Indeed, NIX was found to be necessary for LC3 activation following Δψ<sub>m</sub> loss and parkin recruitment to the mitochondria, suggesting it might be essential to the parkin/PINK1 mitophagy pathway (<xref ref-type="bibr" rid="B63">63</xref>). This also raises the possibility that parkin and PINK1 function in a programed mitophagy pathway, although it would be unlikely to involve RBCs, as one would then expect parkin- or PINK1-associated PD patients to present with anemia (<xref ref-type="bibr" rid="B68">68</xref>).</p><table-wrap id="T1" position="float"><label>Table 1</label><caption><p><bold>Comparison of mitophagy pathways</bold>.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">Parkin/PINK1</th><th align="left" rowspan="1" colspan="1">Reticulocytes</th><th align="left" rowspan="1" colspan="1">Fertilized oocyte</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Dependence on ATG family proteins</td><td align="left" rowspan="1" colspan="1">Yes (LC3, ATG5)</td><td align="left" rowspan="1" colspan="1">Yes (LC3)</td><td align="left" rowspan="1" colspan="1">Yes (LGG-1)</td></tr><tr><td align="left" rowspan="1" colspan="1">Ubiquitination of mitochondria prior to autophagy</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">N/A</td><td align="left" rowspan="1" colspan="1">No</td></tr><tr><td align="left" rowspan="1" colspan="1">Known, essential pathway components</td><td align="left" rowspan="1" colspan="1">Parkin, PINK1, HDAC6 (<xref ref-type="bibr" rid="B88">88</xref>), Ubiquitin-proteasome system (UPS) (<xref ref-type="bibr" rid="B48">48</xref>), VDAC1, 2, and 3 (<xref ref-type="bibr" rid="B89">89</xref>), Ambra1 (<xref ref-type="bibr" rid="B90">90</xref>), NIX (<xref ref-type="bibr" rid="B63">63</xref>)</td><td align="left" rowspan="1" colspan="1">NIX</td><td align="left" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" rowspan="1" colspan="1">Loss of ΔΨ<sub>m</sub></td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" rowspan="1" colspan="1">Complete loss of mitochondria</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" rowspan="1" colspan="1">Type of mitophagy</td><td align="left" rowspan="1" colspan="1">Reactionary (?)</td><td align="left" rowspan="1" colspan="1">Programed</td><td align="left" rowspan="1" colspan="1">Programed</td></tr></tbody></table></table-wrap><p>A second type of programed mitophagy consists of the elimination of paternal mitochondria in the fertilized oocyte (<xref ref-type="bibr" rid="B69">69</xref>). While the notion that mitochondrial DNA is inherited uniquely from the mother has been long established, only recently have studies in <italic>C. elegans</italic> found that the degradation of paternal mitochondria, as well as its mtDNA, occurs through mitophagy (<xref ref-type="bibr" rid="B70">70</xref><xref ref-type="bibr" rid="B71"></xref>–<xref ref-type="bibr" rid="B72">72</xref>). Whereas autophagy of paternal mitochondria was demonstrated to rely on the ATG-associated machinery for mitochondrial degradation, it was also shown that mitochondrial ubiquitination does not appear prior to engulfment, as opposed to mitophagy occurring during reticulocyte maturation and the parkin/PINK1 pathway (Table <xref ref-type="table" rid="T1">1</xref>). However, further work on autophagy of paternal mitochondria, clarifying whether mitochondria are depolarized prior to engulfment, remains to be done; it would be interesting to see if parkin and PINK1 are implicated in this pathway, possibly by examining the occurrence of autophagy of paternal mitochondria in fertilized ova of parkin- or PINK1-null mice. Interestingly, parkin- and PINK1-null flies both show mitochondrial abnormalities in embryonic development, characterized by swollen or vacuolated nebenkern – spheres encompassing two giant mitochondria in the developing fly spermatid – which result in male sterility (<xref ref-type="bibr" rid="B73">73</xref><xref ref-type="bibr" rid="B74"></xref>–<xref ref-type="bibr" rid="B75">75</xref>). These findings suggest that, in spermatogenesis, parkin and PINK1 may have a role in mitophagy-related events.</p><p>In essence, it seems that many mitophagic pathways utilize the canonical ATG-associated machinery, yet differ both in the manner through which mitochondria are signaled for autophagosomal engulfment and in upstream signaling mechanisms. In the case of parkin-/PINK1-dependent mitophagy, it is the latter that is poorly defined, and it is plausible that a programed mitophagic pathway, utilizing parkin and PINK1, exists in mammals and contributes to PD pathogenesis. In addition, we have already described that PINK1 can accumulate on mitochondria upon disruption of mitochondrial import in the absence of depolarization (<xref ref-type="bibr" rid="B39">39</xref>), suggesting that several upstream mechanisms may impinge on a canonical, programed parkin/PINK1 mitophagic pathway.</p></sec><sec id="S5"><title>Mitophagy in Parkinson’s Disease</title><p>Although studies examining parkin-/PINK1-dependent mitophagy as a quality control mechanism have relied heavily on the use of chemical uncouplers in heterologous cell culture (<xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B43">43</xref>, <xref ref-type="bibr" rid="B45">45</xref>, <xref ref-type="bibr" rid="B47">47</xref>, <xref ref-type="bibr" rid="B50">50</xref>), the existence and relevance of such a pathway in neurons has remained elusive, based on a handful of studies relying predominantly on parkin overexpression (<xref ref-type="bibr" rid="B76">76</xref><xref ref-type="bibr" rid="B77"></xref>–<xref ref-type="bibr" rid="B78">78</xref>). Alarmingly, other groups were unable to show recruitment of overexpressed parkin in neurons following mitochondrial depolarization (<xref ref-type="bibr" rid="B79">79</xref>), or showed that endogenous parkin failed to mediate mitophagy in neurons and cultured cells (<xref ref-type="bibr" rid="B80">80</xref>).</p><p>As described previously, complete autophagy of the mitochondrial network can occur in many cell types in response to intrinsic or extrinsic signals. Neurons, however, cannot switch to glycolytic metabolism (as an ATP-generating mechanism) during acute mitochondrial stress, and hence are utterly dependent on mitochondria for energy production (<xref ref-type="bibr" rid="B81">81</xref>, <xref ref-type="bibr" rid="B82">82</xref>). Therefore, it is unlikely that molecular pathways have evolved to remove the whole mitochondrial network following mitochondrial damage in neurons. Moreover, it has been shown that neurons divert glucose away from glycolysis to the pentose phosphate pathway – in order to maintain a high level of reduced glutathione – and instead generate ATP predominantly through OXPHOS (<xref ref-type="bibr" rid="B83">83</xref>, <xref ref-type="bibr" rid="B84">84</xref>). As such, disruption of the OXPHOS process by uncouplers or other mitochondrial toxins results in a bioenergetic crisis inherent to neurons, and may contribute to the ambiguity surrounding findings concerning the PINK1/parkin pathway obtained from this cell type.</p><p>Thus, two important questions arise from the controversy surrounding the relevance of the PINK1/parkin pathway in neurons: (1) whether or not parkin is recruited to depolarized mitochondria in these cells and, if so, (2) what is the physiological role of this recruitment in neurons? While parkin recruitment was shown to be robust and reproducible in immortalized cells, the data indicate that this is more variable in neurons. This is not so surprising since neuronal culture protocols carry many more variables than those for immortalized cells. When analyzing data from the five studies on parkin-/PINK1-dependent mitophagy in neurons (Table <xref ref-type="table" rid="T2">2</xref>), we find that many components of neuronal media could influence parkin translocation. Cai and colleagues used inhibitors of apoptosis in their neuronal culture (the caspase inhibitor Z-VAD-FMK) to counter the effects of high doses of chemical uncouplers triggering apoptosis in an environment devoid of protective glia. While these conditions do lead to parkin translocation in neurons, they may also mask the normal physiological reaction of neurons to gross depolarization of the mitochondrial network. It is unlikely that neurons have evolved to adapt to this type of insult, and apoptosis may be the physiological response. Interestingly, in the study (<xref ref-type="bibr" rid="B77">77</xref>) that showed the highest percentage of parkin translocation (about 70%), it was found that recruitment was dependent on the absence of antioxidants (in the form of the B-27 supplement) in the media. Taken together, these factors might explain why some groups (<xref ref-type="bibr" rid="B79">79</xref>) were not able to detect significant parkin translocation upon mitochondrial depolarization in neurons. Importantly, parkin translocation was also much slower (12–24 h) in the study that used B-27 than in studies without it (4 h). This indicates that neuronal cultures containing antioxidant supplements may counteract the action of chemical uncouplers. It would however be important to determine if, under growth conditions lacking antioxidants, neurons can survive over long time periods following mitochondrial depolarization. In light of these recent studies, we conclude that parkin can translocate to mitochondria in neurons following depolarization, given the proper culture conditions. However, most of these studies did not quantify mitophagy following parkin translocation (<xref ref-type="bibr" rid="B76">76</xref><xref ref-type="bibr" rid="B77"></xref>–<xref ref-type="bibr" rid="B78">78</xref>). While Seibler and colleagues found that parkin-positive cells have reduced mitochondrial DNA copy numbers after exposure to CCCP, they did not rule out decreased mitochondrial biogenesis as a possible mechanism. This raises the question of whether parkin translocation proceeds to mitophagy in neurons, or plays another role. Rakovic and colleagues addressed this question by looking at the degradation of a number of mitochondrial proteins both at the outer membrane, the inner membrane, and the matrix. Surprisingly, they found that even when overexpressing parkin in induced pluripotent stem (iPS) cell-derived dopaminergic neurons, parkin does not promote mitophagy upon mitochondria depolarization. However, given that the kinetics of parkin recruitment to mitochondria seem considerably slower in neurons (70% recruitment at 4 h) than in immortalized cells (100% at 2 h) (Table <xref ref-type="table" rid="T3">3</xref>), it is plausible that mitophagy may proceed more slowly and may not be detectable at 16 h with the 1 μM valinomycin used by Rakovic and colleagues. Again, one obvious issue may be that incubating neuronal cultures with chemical uncouplers for an extended period may induce apoptosis. Adding apoptotic inhibitors may circumvent this limitation, allowing for the study of parkin-dependent mitophagy in neurons on a longer time scale, as shown by Cai and colleagues. Whereas this allowed them to show colocalization between autophagic markers and mitochondria in isolated events, Cai and colleagues did not quantify them in parkin-overexpressing versus mock-transfected neurons.</p><table-wrap id="T2" position="float"><label>Table 2</label><caption><p><bold>Comparison of data on Parkin/PINK1-dependent mitophagy in neurons</bold>.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">Cai et al. (<xref ref-type="bibr" rid="B76">76</xref>)</th><th align="left" rowspan="1" colspan="1">Joselin et al. (<xref ref-type="bibr" rid="B77">77</xref>)</th><th align="left" rowspan="1" colspan="1">Seibler et al. (<xref ref-type="bibr" rid="B78">78</xref>)</th><th align="left" rowspan="1" colspan="1">Van Laar et al. (<xref ref-type="bibr" rid="B79">79</xref>)</th><th align="left" rowspan="1" colspan="1">Rakovic et al. (<xref ref-type="bibr" rid="B80">80</xref>)</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Neuronal type</td><td align="left" rowspan="1" colspan="1">Cortical</td><td align="left" rowspan="1" colspan="1">Cortical</td><td align="left" rowspan="1" colspan="1">IPS-derived dopaminergic neurons</td><td align="left" rowspan="1" colspan="1">Cortical</td><td align="left" rowspan="1" colspan="1">IPS-derived dopaminergic neurons</td></tr><tr><td align="left" rowspan="1" colspan="1">Glial bed</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td></tr><tr><td align="left" rowspan="1" colspan="1">Days <italic>in vitro</italic></td><td align="left" rowspan="1" colspan="1">8–10</td><td align="left" rowspan="1" colspan="1">8</td><td align="left" rowspan="1" colspan="1">–</td><td align="left" rowspan="1" colspan="1">9</td><td align="left" rowspan="1" colspan="1">–</td></tr><tr><td align="left" rowspan="1" colspan="1">Apoptotic inhibitors</td><td align="left" rowspan="1" colspan="1">Z-VAD-FMK</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td></tr><tr><td align="left" rowspan="1" colspan="1">B-27</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">–</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" rowspan="1" colspan="1">Uncoupling agent + time of exposure</td><td align="left" rowspan="1" colspan="1">10 μM CCCP 24 h</td><td align="left" rowspan="1" colspan="1">5 μM CCCP 4 h</td><td align="left" rowspan="1" colspan="1">1 μM Valinomycin 12 h</td><td align="left" rowspan="1" colspan="1">10 μM CCCP 6 h</td><td align="left" rowspan="1" colspan="1">1 μM Valinomycin 12 h</td></tr><tr><td align="left" rowspan="1" colspan="1">% Cells with parkin recruitment</td><td align="left" rowspan="1" colspan="1">30%</td><td align="left" rowspan="1" colspan="1">70%</td><td align="left" rowspan="1" colspan="1">N/A (increased colocalization)</td><td align="left" rowspan="1" colspan="1">No CCCP effect 25% basal</td><td align="left" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" rowspan="1" colspan="1">Quantified parkin-dependent mitophagy</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">No (reduced mtDNA copy numbers)</td><td align="left" rowspan="1" colspan="1">N/A</td><td align="left" rowspan="1" colspan="1">Yes (no parkin-dependent mitophagy)</td></tr><tr><td align="left" rowspan="1" colspan="1">Endogenous parkin recruitment</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">N/A</td><td align="left" rowspan="1" colspan="1">N/A</td><td align="left" rowspan="1" colspan="1">No</td><td align="left" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" rowspan="1" colspan="1">PINK1 dependence</td><td align="left" rowspan="1" colspan="1">N/A</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">N/A</td><td align="left" rowspan="1" colspan="1">Yes</td></tr></tbody></table></table-wrap><table-wrap id="T3" position="float"><label>Table 3</label><caption><p><bold>Comparison of parkin recruitment in immortalized cells versus neurons</bold>.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">Immortalized Cells (HeLa, Hek293T, SH-SY5Y, MEFs)</th><th align="left" rowspan="1" colspan="1">Neurons (primary, IPS-derived)</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Mean time of parkin recruitment upon ΔΨ<sub>m</sub> depolarization (more than 30% cell with parkin on mitochondria)</td><td align="left" rowspan="1" colspan="1">30 min (<xref ref-type="bibr" rid="B50">50</xref>)</td><td align="left" rowspan="1" colspan="1">4 h (<xref ref-type="bibr" rid="B77">77</xref>); 6 h (<xref ref-type="bibr" rid="B79">79</xref>); 12 h (<xref ref-type="bibr" rid="B78">78</xref>); 24 h (<xref ref-type="bibr" rid="B76">76</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Dependence on PINK1</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" rowspan="1" colspan="1">Survival after long-term exposure to chemical uncouplers</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">N/A; use of apoptotic inhibitors (<xref ref-type="bibr" rid="B76">76</xref>)</td></tr><tr><td align="left" rowspan="1" colspan="1">Complete removal of mitochondria</td><td align="left" rowspan="1" colspan="1">Yes</td><td align="left" rowspan="1" colspan="1">N/A</td></tr></tbody></table></table-wrap><p>To overcome the limitations of <italic>in vitro</italic> neuronal cultures, Sterky and colleagues crossed MitoPark mice – which develop progressive parkinsonism and mitochondrial abnormalities stemming from the ablated expression of mitochondrial transcription factor A in dopaminergic neurons (<xref ref-type="bibr" rid="B85">85</xref>) – with parkin knockout mice. These mice did not show increased neurodegeneration or accumulation of damaged mitochondria, suggesting that parkin had no role in degrading damaged mitochondria (<xref ref-type="bibr" rid="B86">86</xref>). Moreover, they overexpressed parkin in the MitoPark mouse and found that parkin was not recruited to mitochondria at the steady-state. While these data suggest that parkin may not be involved in mitophagy in the brain <italic>in vivo</italic>, it is noteworthy that the mitochondrial defects of MitoPark mice have not been fully characterized, and, as such, the mitochondria of these mice may not be sufficiently depolarized to stabilize PINK1 levels and trigger parkin recruitment. Interestingly, a recent study by Vincow and colleagues demonstrated that parkin null flies exhibit a slower turnover of mitochondrial proteins (<xref ref-type="bibr" rid="B87">87</xref>). Moreover, they showed that electron transport chain (ETC) protein turnover is especially affected in both parkin and PINK1 single-null flies, suggesting that, under physiological conditions, parkin and PINK1 might have a specific role in regulating the levels of ETC proteins, as opposed to the complete removal of mitochondria following depolarization in cell lines. In light of these results, it is clear that further studies will be required to test whether parkin promotes mitophagy in neurons and what are its consequences <italic>in vivo</italic>.</p></sec><sec sec-type="conclusions" id="S6"><title>Conclusion</title><p>Parkin and PINK1 are the first two PD-associated genes to be implicated in a common genetic pathway. More specifically, the association of parkin and PINK1 in a common mitochondrial quality control pathway has consolidated the hypothesis that mitochondrial defects are central to PD pathogenesis. However, the physiological relevance of such a pathway in neurons requires further investigation. Moreover, neuronal parkin and PINK1 may play roles in mitochondrial homeostasis other than degrading damaged mitochondria, such as regulating ETC protein turnover. Upon review of the few, pioneering studies that have aimed to clarify these questions, we conclude that, although it is robust and implicates many other players subsequent to parkin recruitment, the parkin/PINK1 mitophagy pathway still lacks proper upstream signaling characterization. This is reflected in the inability to find a consensus on the proper conditions with which to study this pathway in a more disease-relevant cell type. We also conclude that, while redistribution of parkin to depolarized mitochondria has now been shown in neurons, the physiological role of such recruitment – specifically, whether or not this proceeds to mitophagy – remains elusive. By understanding the physiological function of parkin and PINK1 in neurons, future studies will undoubtedly reveal key molecular mechanisms underlying neurodegeneration and hence novel therapeutic targets for the treatment of PD.</p></sec><sec id="S7"><title>Conflict of Interest Statement</title><p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec></body><back><ref-list><title>References</title><ref id="B1"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lill</surname><given-names>CM</given-names></name><name><surname>Bertram</surname><given-names>L</given-names></name></person-group><article-title>Towards unveiling the genetics of neurodegenerative diseases</article-title>. <source>Semin Neurol</source> (<year>2011</year>) <volume>31</volume>:<fpage>531</fpage>–<lpage>41</lpage><pub-id pub-id-type="doi">10.1055/s-0031-1299791</pub-id><pub-id pub-id-type="pmid">22266890</pub-id></mixed-citation></ref><ref id="B2"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Karbowski</surname><given-names>M</given-names></name><name><surname>Neutzner</surname><given-names>A</given-names></name></person-group><article-title>Neurodegeneration as a consequence of failed mitochondrial maintenance</article-title>. <source>Acta Neuropathol</source> (<year>2012</year>) <volume>123</volume>:<fpage>157</fpage>–<lpage>71</lpage><pub-id pub-id-type="doi">10.1007/s00401-011-0921-0</pub-id><pub-id pub-id-type="pmid">22143516</pub-id></mixed-citation></ref><ref id="B3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Langston</surname><given-names>JW</given-names></name><name><surname>Ballard</surname><given-names>P</given-names></name><name><surname>Tetrud</surname><given-names>JW</given-names></name><name><surname>Irwin</surname><given-names>I</given-names></name></person-group><article-title>Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis</article-title>. <source>Science</source> (<year>1983</year>) <volume>219</volume>:<fpage>979</fpage>–<lpage>80</lpage><pub-id pub-id-type="doi">10.1126/science.6823561</pub-id><pub-id pub-id-type="pmid">6823561</pub-id></mixed-citation></ref><ref id="B4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schapira</surname><given-names>AH</given-names></name></person-group><article-title>Mitochondria in the aetiology and pathogenesis of Parkinson’s disease</article-title>. <source>Lancet Neurol</source> (<year>2008</year>) <volume>7</volume>:<fpage>97</fpage>–<lpage>109</lpage><pub-id pub-id-type="doi">10.1016/S1474-4422(07)70327-7</pub-id><pub-id pub-id-type="pmid">18093566</pub-id></mixed-citation></ref><ref id="B5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mann</surname><given-names>VM</given-names></name><name><surname>Cooper</surname><given-names>JM</given-names></name><name><surname>Krige</surname><given-names>D</given-names></name><name><surname>Daniel</surname><given-names>SE</given-names></name><name><surname>Schapira</surname><given-names>AH</given-names></name><name><surname>Marsden</surname><given-names>CD</given-names></name></person-group><article-title>Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson’s disease</article-title>. <source>Brain</source> (<year>1992</year>) <volume>115</volume>(<issue>Pt 2</issue>):<fpage>333</fpage>–<lpage>42</lpage><pub-id pub-id-type="doi">10.1093/brain/115.2.333</pub-id><pub-id pub-id-type="pmid">1606472</pub-id></mixed-citation></ref><ref id="B6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bender</surname><given-names>A</given-names></name><name><surname>Krishnan</surname><given-names>KJ</given-names></name><name><surname>Morris</surname><given-names>CM</given-names></name><name><surname>Taylor</surname><given-names>GA</given-names></name><name><surname>Reeve</surname><given-names>AK</given-names></name><name><surname>Perry</surname><given-names>RH</given-names></name><etal></etal></person-group><article-title>High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease</article-title>. <source>Nat Genet</source> (<year>2006</year>) <volume>38</volume>:<fpage>515</fpage>–<lpage>7</lpage><pub-id pub-id-type="doi">10.1038/ng1769</pub-id><pub-id pub-id-type="pmid">16604074</pub-id></mixed-citation></ref><ref id="B7"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kraytsberg</surname><given-names>Y</given-names></name><name><surname>Kudryavtseva</surname><given-names>E</given-names></name><name><surname>McKee</surname><given-names>AC</given-names></name><name><surname>Geula</surname><given-names>C</given-names></name><name><surname>Kowall</surname><given-names>NW</given-names></name><name><surname>Khrapko</surname><given-names>K</given-names></name></person-group><article-title>Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons</article-title>. <source>Nat Genet</source> (<year>2006</year>) <volume>38</volume>:<fpage>518</fpage>–<lpage>20</lpage><pub-id pub-id-type="doi">10.1038/ng1778</pub-id><pub-id pub-id-type="pmid">16604072</pub-id></mixed-citation></ref><ref id="B8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nunnari</surname><given-names>J</given-names></name><name><surname>Suomalainen</surname><given-names>A</given-names></name></person-group><article-title>Mitochondria: in sickness and in health</article-title>. <source>Cell</source> (<year>2012</year>) <volume>148</volume>:<fpage>1145</fpage>–<lpage>59</lpage><pub-id pub-id-type="doi">10.1016/j.cell.2012.02.035</pub-id><pub-id pub-id-type="pmid">22424226</pub-id></mixed-citation></ref><ref id="B9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Westermann</surname><given-names>B</given-names></name></person-group><article-title>Mitochondrial fusion and fission in cell life and death</article-title>. <source>Nat Rev Mol Cell Biol</source> (<year>2010</year>) <volume>11</volume>:<fpage>872</fpage>–<lpage>84</lpage><pub-id pub-id-type="doi">10.1038/nrm3013</pub-id><pub-id pub-id-type="pmid">21102612</pub-id></mixed-citation></ref><ref id="B10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tatsuta</surname><given-names>T</given-names></name><name><surname>Langer</surname><given-names>T</given-names></name></person-group><article-title>Quality control of mitochondria: protection against neurodegeneration and ageing</article-title>. <source>EMBO J</source> (<year>2008</year>) <volume>27</volume>:<fpage>306</fpage>–<lpage>14</lpage><pub-id pub-id-type="doi">10.1038/sj.emboj.7601972</pub-id><pub-id pub-id-type="pmid">18216873</pub-id></mixed-citation></ref><ref id="B11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ashrafi</surname><given-names>G</given-names></name><name><surname>Schwarz</surname><given-names>TL</given-names></name></person-group><article-title>The pathways of mitophagy for quality control and clearance of mitochondria</article-title>. <source>Cell Death Differ</source> (<year>2013</year>) <volume>20</volume>:<fpage>31</fpage>–<lpage>42</lpage><pub-id pub-id-type="doi">10.1038/cdd.2012.81</pub-id><pub-id pub-id-type="pmid">22743996</pub-id></mixed-citation></ref><ref id="B12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shutt</surname><given-names>TE</given-names></name><name><surname>McBride</surname><given-names>HM</given-names></name></person-group><article-title>Staying cool in difficult times: mitochondrial dynamics, quality control and the stress response</article-title>. <source>Biochim Biophys Acta</source> (<year>2013</year>) <volume>1833</volume>:<fpage>417</fpage>–<lpage>24</lpage><pub-id pub-id-type="doi">10.1016/j.bbamcr.2012.05.024</pub-id><pub-id pub-id-type="pmid">22683990</pub-id></mixed-citation></ref><ref id="B13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Soubannier</surname><given-names>V</given-names></name><name><surname>McLelland</surname><given-names>GL</given-names></name><name><surname>Zunino</surname><given-names>R</given-names></name><name><surname>Braschi</surname><given-names>E</given-names></name><name><surname>Rippstein</surname><given-names>P</given-names></name><name><surname>Fon</surname><given-names>EA</given-names></name><etal></etal></person-group><article-title>A vesicular transport pathway shuttles cargo from mitochondria to lysosomes</article-title>. <source>Curr Biol</source> (<year>2012</year>) <volume>22</volume>:<fpage>135</fpage>–<lpage>41</lpage><pub-id pub-id-type="doi">10.1016/j.cub.2011.11.057</pub-id><pub-id pub-id-type="pmid">22226745</pub-id></mixed-citation></ref><ref id="B14"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Soubannier</surname><given-names>V</given-names></name><name><surname>Rippstein</surname><given-names>P</given-names></name><name><surname>Kaufman</surname><given-names>BA</given-names></name><name><surname>Shoubridge</surname><given-names>EA</given-names></name><name><surname>McBride</surname><given-names>HM</given-names></name></person-group><article-title>Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo</article-title>. <source>PLoS ONE</source> (<year>2012</year>) <volume>7</volume>:<fpage>e52830</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0052830</pub-id><pub-id pub-id-type="pmid">23300790</pub-id></mixed-citation></ref><ref id="B15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>CS</given-names></name><name><surname>Gertler</surname><given-names>TS</given-names></name><name><surname>Surmeier</surname><given-names>DJ</given-names></name></person-group><article-title>Calcium homeostasis, selective vulnerability and Parkinson’s disease</article-title>. <source>Trends Neurosci</source> (<year>2009</year>) <volume>32</volume>:<fpage>249</fpage>–<lpage>56</lpage><pub-id pub-id-type="doi">10.1016/j.tins.2009.01.006</pub-id><pub-id pub-id-type="pmid">19307031</pub-id></mixed-citation></ref><ref id="B16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baxter</surname><given-names>RV</given-names></name><name><surname>Ben Othmane</surname><given-names>K</given-names></name><name><surname>Rochelle</surname><given-names>JM</given-names></name><name><surname>Stajich</surname><given-names>JE</given-names></name><name><surname>Hulette</surname><given-names>C</given-names></name><name><surname>Dew-Knight</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21</article-title>. <source>Nat Genet</source> (<year>2002</year>) <volume>30</volume>:<fpage>21</fpage>–<lpage>2</lpage><pub-id pub-id-type="doi">10.1038/ng796</pub-id><pub-id pub-id-type="pmid">11743579</pub-id></mixed-citation></ref><ref id="B17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cuesta</surname><given-names>A</given-names></name><name><surname>Pedrola</surname><given-names>L</given-names></name><name><surname>Sevilla</surname><given-names>T</given-names></name><name><surname>Garcia-Planells</surname><given-names>J</given-names></name><name><surname>Chumillas</surname><given-names>MJ</given-names></name><name><surname>Mayordomo</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease</article-title>. <source>Nat Genet</source> (<year>2002</year>) <volume>30</volume>:<fpage>22</fpage>–<lpage>5</lpage><pub-id pub-id-type="doi">10.1038/ng798</pub-id><pub-id pub-id-type="pmid">11743580</pub-id></mixed-citation></ref><ref id="B18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Delettre</surname><given-names>C</given-names></name><name><surname>Lenaers</surname><given-names>G</given-names></name><name><surname>Griffoin</surname><given-names>JM</given-names></name><name><surname>Gigarel</surname><given-names>N</given-names></name><name><surname>Lorenzo</surname><given-names>C</given-names></name><name><surname>Belenguer</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy</article-title>. <source>Nat Genet</source> (<year>2000</year>) <volume>26</volume>:<fpage>207</fpage>–<lpage>10</lpage><pub-id pub-id-type="doi">10.1038/79936</pub-id><pub-id pub-id-type="pmid">11017079</pub-id></mixed-citation></ref><ref id="B19"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Di Bella</surname><given-names>D</given-names></name><name><surname>Lazzaro</surname><given-names>F</given-names></name><name><surname>Brusco</surname><given-names>A</given-names></name><name><surname>Plumari</surname><given-names>M</given-names></name><name><surname>Battaglia</surname><given-names>G</given-names></name><name><surname>Pastore</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28</article-title>. <source>Nat Genet</source> (<year>2010</year>) <volume>42</volume>:<fpage>313</fpage>–<lpage>21</lpage><pub-id pub-id-type="doi">10.1038/ng.544</pub-id><pub-id pub-id-type="pmid">20208537</pub-id></mixed-citation></ref><ref id="B20"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Edener</surname><given-names>U</given-names></name><name><surname>Wollner</surname><given-names>J</given-names></name><name><surname>Hehr</surname><given-names>U</given-names></name><name><surname>Kohl</surname><given-names>Z</given-names></name><name><surname>Schilling</surname><given-names>S</given-names></name><name><surname>Kreuz</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation</article-title>. <source>Eur J Hum Genet</source> (<year>2010</year>) <volume>18</volume>:<fpage>965</fpage>–<lpage>8</lpage><pub-id pub-id-type="doi">10.1038/ejhg.2010.40</pub-id><pub-id pub-id-type="pmid">20354562</pub-id></mixed-citation></ref><ref id="B21"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shimura</surname><given-names>H</given-names></name><name><surname>Hattori</surname><given-names>N</given-names></name><name><surname>Kubo</surname><given-names>S</given-names></name><name><surname>Mizuno</surname><given-names>Y</given-names></name><name><surname>Asakawa</surname><given-names>S</given-names></name><name><surname>Minoshima</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase</article-title>. <source>Nat Genet</source> (<year>2000</year>) <volume>25</volume>:<fpage>302</fpage>–<lpage>5</lpage><pub-id pub-id-type="doi">10.1038/77060</pub-id><pub-id pub-id-type="pmid">10888878</pub-id></mixed-citation></ref><ref id="B22"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Valente</surname><given-names>EM</given-names></name><name><surname>Abou-Sleiman</surname><given-names>PM</given-names></name><name><surname>Caputo</surname><given-names>V</given-names></name><name><surname>Muqit</surname><given-names>MM</given-names></name><name><surname>Harvey</surname><given-names>K</given-names></name><name><surname>Gispert</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Hereditary early-onset Parkinson’s disease caused by mutations in PINK1</article-title>. <source>Science</source> (<year>2004</year>) <volume>304</volume>:<fpage>1158</fpage>–<lpage>60</lpage><pub-id pub-id-type="doi">10.1126/science.1096284</pub-id><pub-id pub-id-type="pmid">15087508</pub-id></mixed-citation></ref><ref id="B23"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zuchner</surname><given-names>S</given-names></name><name><surname>Mersiyanova</surname><given-names>IV</given-names></name><name><surname>Muglia</surname><given-names>M</given-names></name><name><surname>Bissar-Tadmouri</surname><given-names>N</given-names></name><name><surname>Rochelle</surname><given-names>J</given-names></name><name><surname>Dadali</surname><given-names>EL</given-names></name><etal></etal></person-group><article-title>Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A</article-title>. <source>Nat Genet</source> (<year>2004</year>) <volume>36</volume>:<fpage>449</fpage>–<lpage>51</lpage><pub-id pub-id-type="doi">10.1038/ng1341</pub-id><pub-id pub-id-type="pmid">15064763</pub-id></mixed-citation></ref><ref id="B24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schon</surname><given-names>EA</given-names></name><name><surname>Przedborski</surname><given-names>S</given-names></name></person-group><article-title>Mitochondria: the next (neurode)generation</article-title>. <source>Neuron</source> (<year>2011</year>) <volume>70</volume>:<fpage>1033</fpage>–<lpage>53</lpage><pub-id pub-id-type="doi">10.1016/j</pub-id><pub-id pub-id-type="pmid">21689593</pub-id></mixed-citation></ref><ref id="B25"><label>25</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Deng</surname><given-names>H</given-names></name><name><surname>Dodson</surname><given-names>MW</given-names></name><name><surname>Huang</surname><given-names>H</given-names></name><name><surname>Guo</surname><given-names>M</given-names></name></person-group><article-title>The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in <italic>Drosophila</italic></article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2008</year>) <volume>105</volume>:<fpage>14503</fpage>–<lpage>8</lpage><pub-id pub-id-type="doi">10.1073/pnas.0803998105</pub-id><pub-id pub-id-type="pmid">18799731</pub-id></mixed-citation></ref><ref id="B26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Poole</surname><given-names>AC</given-names></name><name><surname>Thomas</surname><given-names>RE</given-names></name><name><surname>Andrews</surname><given-names>LA</given-names></name><name><surname>McBride</surname><given-names>HM</given-names></name><name><surname>Whitworth</surname><given-names>AJ</given-names></name><name><surname>Pallanck</surname><given-names>LJ</given-names></name></person-group><article-title>The PINK1/Parkin pathway regulates mitochondrial morphology</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2008</year>) <volume>105</volume>:<fpage>1638</fpage>–<lpage>43</lpage><pub-id pub-id-type="doi">10.1073/pnas.0709336105</pub-id><pub-id pub-id-type="pmid">18230723</pub-id></mixed-citation></ref><ref id="B27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Exner</surname><given-names>N</given-names></name><name><surname>Treske</surname><given-names>B</given-names></name><name><surname>Paquet</surname><given-names>D</given-names></name><name><surname>Holmstrom</surname><given-names>K</given-names></name><name><surname>Schiesling</surname><given-names>C</given-names></name><name><surname>Gispert</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin</article-title>. <source>J Neurosci</source> (<year>2007</year>) <volume>27</volume>:<fpage>12413</fpage>–<lpage>8</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.0719-07.2007</pub-id><pub-id pub-id-type="pmid">17989306</pub-id></mixed-citation></ref><ref id="B28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lutz</surname><given-names>AK</given-names></name><name><surname>Exner</surname><given-names>N</given-names></name><name><surname>Fett</surname><given-names>ME</given-names></name><name><surname>Schlehe</surname><given-names>JS</given-names></name><name><surname>Kloos</surname><given-names>K</given-names></name><name><surname>Lammermann</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation</article-title>. <source>J Biol Chem</source> (<year>2009</year>) <volume>284</volume>:<fpage>22938</fpage>–<lpage>51</lpage><pub-id pub-id-type="doi">10.1074/jbc.M109.035774</pub-id><pub-id pub-id-type="pmid">19546216</pub-id></mixed-citation></ref><ref id="B29"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mortiboys</surname><given-names>H</given-names></name><name><surname>Thomas</surname><given-names>KJ</given-names></name><name><surname>Koopman</surname><given-names>WJ</given-names></name><name><surname>Klaffke</surname><given-names>S</given-names></name><name><surname>Abou-Sleiman</surname><given-names>P</given-names></name><name><surname>Olpin</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts</article-title>. <source>Ann Neurol</source> (<year>2008</year>) <volume>64</volume>:<fpage>555</fpage>–<lpage>65</lpage><pub-id pub-id-type="doi">10.1002/ana.21492</pub-id><pub-id pub-id-type="pmid">19067348</pub-id></mixed-citation></ref><ref id="B30"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amo</surname><given-names>T</given-names></name><name><surname>Sato</surname><given-names>S</given-names></name><name><surname>Saiki</surname><given-names>S</given-names></name><name><surname>Wolf</surname><given-names>AM</given-names></name><name><surname>Toyomizu</surname><given-names>M</given-names></name><name><surname>Gautier</surname><given-names>CA</given-names></name><etal></etal></person-group><article-title>Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to proton leak, but to respiratory chain defects</article-title>. <source>Neurobiol Dis</source> (<year>2011</year>) <volume>41</volume>:<fpage>111</fpage>–<lpage>8</lpage><pub-id pub-id-type="doi">10.1016/j.nbd.2010.08.027</pub-id><pub-id pub-id-type="pmid">20817094</pub-id></mixed-citation></ref><ref id="B31"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gautier</surname><given-names>CA</given-names></name><name><surname>Kitada</surname><given-names>T</given-names></name><name><surname>Shen</surname><given-names>J</given-names></name></person-group><article-title>Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2008</year>) <volume>105</volume>:<fpage>11364</fpage>–<lpage>9</lpage><pub-id pub-id-type="doi">10.1073/pnas.0802076105</pub-id><pub-id pub-id-type="pmid">18687901</pub-id></mixed-citation></ref><ref id="B32"><label>32</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gegg</surname><given-names>ME</given-names></name><name><surname>Cooper</surname><given-names>JM</given-names></name><name><surname>Schapira</surname><given-names>AH</given-names></name><name><surname>Taanman</surname><given-names>JW</given-names></name></person-group><article-title>Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells</article-title>. <source>PLoS ONE</source> (<year>2009</year>) <volume>4</volume>:<fpage>e4756</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0004756</pub-id><pub-id pub-id-type="pmid">19270741</pub-id></mixed-citation></ref><ref id="B33"><label>33</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Morais</surname><given-names>VA</given-names></name><name><surname>Verstreken</surname><given-names>P</given-names></name><name><surname>Roethig</surname><given-names>A</given-names></name><name><surname>Smet</surname><given-names>J</given-names></name><name><surname>Snellinx</surname><given-names>A</given-names></name><name><surname>Vanbrabant</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Parkinson’s disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function</article-title>. <source>EMBO Mol Med</source> (<year>2009</year>) <volume>1</volume>:<fpage>99</fpage>–<lpage>111</lpage><pub-id pub-id-type="doi">10.1002/emmm.200900006</pub-id><pub-id pub-id-type="pmid">20049710</pub-id></mixed-citation></ref><ref id="B34"><label>34</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vilain</surname><given-names>S</given-names></name><name><surname>Esposito</surname><given-names>G</given-names></name><name><surname>Haddad</surname><given-names>D</given-names></name><name><surname>Schaap</surname><given-names>O</given-names></name><name><surname>Dobreva</surname><given-names>MP</given-names></name><name><surname>Vos</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants</article-title>. <source>PLoS Genet</source> (<year>2012</year>) <volume>8</volume>:<fpage>e1002456</fpage><pub-id pub-id-type="doi">10.1371/journal.pgen.1002456</pub-id><pub-id pub-id-type="pmid">22242018</pub-id></mixed-citation></ref><ref id="B35"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gandhi</surname><given-names>S</given-names></name><name><surname>Wood-Kaczmar</surname><given-names>A</given-names></name><name><surname>Yao</surname><given-names>Z</given-names></name><name><surname>Plun-Favreau</surname><given-names>H</given-names></name><name><surname>Deas</surname><given-names>E</given-names></name><name><surname>Klupsch</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death</article-title>. <source>Mol Cell</source> (<year>2009</year>) <volume>33</volume>:<fpage>627</fpage>–<lpage>38</lpage><pub-id pub-id-type="doi">10.1016/j.molcel.2009.02.013</pub-id><pub-id pub-id-type="pmid">19285945</pub-id></mixed-citation></ref><ref id="B36"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Heeman</surname><given-names>B</given-names></name><name><surname>Van den Haute</surname><given-names>C</given-names></name><name><surname>Aelvoet</surname><given-names>SA</given-names></name><name><surname>Valsecchi</surname><given-names>F</given-names></name><name><surname>Rodenburg</surname><given-names>RJ</given-names></name><name><surname>Reumers</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance</article-title>. <source>J Cell Sci</source> (<year>2011</year>) <volume>124</volume>:<fpage>1115</fpage>–<lpage>25</lpage><pub-id pub-id-type="doi">10.1242/jcs.078303</pub-id><pub-id pub-id-type="pmid">21385841</pub-id></mixed-citation></ref><ref id="B37"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marongiu</surname><given-names>R</given-names></name><name><surname>Spencer</surname><given-names>B</given-names></name><name><surname>Crews</surname><given-names>L</given-names></name><name><surname>Adame</surname><given-names>A</given-names></name><name><surname>Patrick</surname><given-names>C</given-names></name><name><surname>Trejo</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of Parkinson’s disease by disturbing calcium flux</article-title>. <source>J Neurochem</source> (<year>2009</year>) <volume>108</volume>:<fpage>1561</fpage>–<lpage>74</lpage><pub-id pub-id-type="doi">10.1111/j.1471-4159.2009.05932.x</pub-id><pub-id pub-id-type="pmid">19166511</pub-id></mixed-citation></ref><ref id="B38"><label>38</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sandebring</surname><given-names>A</given-names></name><name><surname>Thomas</surname><given-names>KJ</given-names></name><name><surname>Beilina</surname><given-names>A</given-names></name><name><surname>van der Brug</surname><given-names>M</given-names></name><name><surname>Cleland</surname><given-names>MM</given-names></name><name><surname>Ahmad</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1</article-title>. <source>PLoS ONE</source> (<year>2009</year>) <volume>4</volume>:<fpage>e5701</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0005701</pub-id><pub-id pub-id-type="pmid">19492085</pub-id></mixed-citation></ref><ref id="B39"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Greene</surname><given-names>AW</given-names></name><name><surname>Grenier</surname><given-names>K</given-names></name><name><surname>Aguileta</surname><given-names>MA</given-names></name><name><surname>Muise</surname><given-names>S</given-names></name><name><surname>Farazifard</surname><given-names>R</given-names></name><name><surname>Haque</surname><given-names>ME</given-names></name><etal></etal></person-group><article-title>Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment</article-title>. <source>EMBO Rep</source> (<year>2012</year>) <volume>13</volume>:<fpage>378</fpage>–<lpage>85</lpage><pub-id pub-id-type="doi">10.1038/embor.2012.14</pub-id><pub-id pub-id-type="pmid">22354088</pub-id></mixed-citation></ref><ref id="B40"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jin</surname><given-names>SM</given-names></name><name><surname>Lazarou</surname><given-names>M</given-names></name><name><surname>Wang</surname><given-names>C</given-names></name><name><surname>Kane</surname><given-names>LA</given-names></name><name><surname>Narendra</surname><given-names>DP</given-names></name><name><surname>Youle</surname><given-names>RJ</given-names></name></person-group><article-title>Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL</article-title>. <source>J Cell Biol</source> (<year>2010</year>) <volume>191</volume>:<fpage>933</fpage>–<lpage>42</lpage><pub-id pub-id-type="doi">10.1083/jcb.201008084</pub-id><pub-id pub-id-type="pmid">21115803</pub-id></mixed-citation></ref><ref id="B41"><label>41</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lazarou</surname><given-names>M</given-names></name><name><surname>Jin</surname><given-names>SM</given-names></name><name><surname>Kane</surname><given-names>LA</given-names></name><name><surname>Youle</surname><given-names>RJ</given-names></name></person-group><article-title>Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin</article-title>. <source>Dev Cell</source> (<year>2012</year>) <volume>22</volume>:<fpage>320</fpage>–<lpage>33</lpage><pub-id pub-id-type="doi">10.1016/j.devcel.2011.12.014</pub-id><pub-id pub-id-type="pmid">22280891</pub-id></mixed-citation></ref><ref id="B42"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Narendra</surname><given-names>DP</given-names></name><name><surname>Jin</surname><given-names>SM</given-names></name><name><surname>Tanaka</surname><given-names>A</given-names></name><name><surname>Suen</surname><given-names>DF</given-names></name><name><surname>Gautier</surname><given-names>CA</given-names></name><name><surname>Shen</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>PINK1 is selectively stabilized on impaired mitochondria to activate Parkin</article-title>. <source>PLoS Biol</source> (<year>2010</year>) <volume>8</volume>:<fpage>e1000298</fpage><pub-id pub-id-type="doi">10.1371/journal.pbio.1000298</pub-id><pub-id pub-id-type="pmid">20126261</pub-id></mixed-citation></ref><ref id="B43"><label>43</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Geisler</surname><given-names>S</given-names></name><name><surname>Holmstrom</surname><given-names>KM</given-names></name><name><surname>Skujat</surname><given-names>D</given-names></name><name><surname>Fiesel</surname><given-names>FC</given-names></name><name><surname>Rothfuss</surname><given-names>OC</given-names></name><name><surname>Kahle</surname><given-names>PJ</given-names></name><etal></etal></person-group><article-title>PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1</article-title>. <source>Nat Cell Biol</source> (<year>2010</year>) <volume>12</volume>:<fpage>119</fpage>–<lpage>31</lpage><pub-id pub-id-type="doi">10.1038/ncb2012</pub-id><pub-id pub-id-type="pmid">20098416</pub-id></mixed-citation></ref><ref id="B44"><label>44</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lazarou</surname><given-names>M</given-names></name><name><surname>Narendra</surname><given-names>DP</given-names></name><name><surname>Jin</surname><given-names>SM</given-names></name><name><surname>Tekle</surname><given-names>E</given-names></name><name><surname>Banerjee</surname><given-names>S</given-names></name><name><surname>Youle</surname><given-names>RJ</given-names></name></person-group><article-title>PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding</article-title>. <source>J Cell Biol</source> (<year>2013</year>) <volume>200</volume>:<fpage>163</fpage>–<lpage>72</lpage><pub-id pub-id-type="doi">10.1083/jcb.201210111</pub-id><pub-id pub-id-type="pmid">23319602</pub-id></mixed-citation></ref><ref id="B45"><label>45</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsuda</surname><given-names>N</given-names></name><name><surname>Sato</surname><given-names>S</given-names></name><name><surname>Shiba</surname><given-names>K</given-names></name><name><surname>Okatsu</surname><given-names>K</given-names></name><name><surname>Saisho</surname><given-names>K</given-names></name><name><surname>Gautier</surname><given-names>CA</given-names></name><etal></etal></person-group><article-title>PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy</article-title>. <source>J Cell Biol</source> (<year>2010</year>) <volume>189</volume>:<fpage>211</fpage>–<lpage>21</lpage><pub-id pub-id-type="doi">10.1083/jcb.200910140</pub-id><pub-id pub-id-type="pmid">20404107</pub-id></mixed-citation></ref><ref id="B46"><label>46</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shiba-Fukushima</surname><given-names>K</given-names></name><name><surname>Imai</surname><given-names>Y</given-names></name><name><surname>Yoshida</surname><given-names>S</given-names></name><name><surname>Ishihama</surname><given-names>Y</given-names></name><name><surname>Kanao</surname><given-names>T</given-names></name><name><surname>Sato</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy</article-title>. <source>Sci Rep</source> (<year>2012</year>) <volume>2</volume>:<fpage>1002</fpage><pub-id pub-id-type="doi">10.1038/srep01002</pub-id><pub-id pub-id-type="pmid">23256036</pub-id></mixed-citation></ref><ref id="B47"><label>47</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vives-Bauza</surname><given-names>C</given-names></name><name><surname>Zhou</surname><given-names>C</given-names></name><name><surname>Huang</surname><given-names>Y</given-names></name><name><surname>Cui</surname><given-names>M</given-names></name><name><surname>de Vries</surname><given-names>RL</given-names></name><name><surname>Kim</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>PINK1-dependent recruitment of Parkin to mitochondria in mitophagy</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2010</year>) <volume>107</volume>:<fpage>378</fpage>–<lpage>83</lpage><pub-id pub-id-type="doi">10.1073/pnas.0911187107</pub-id><pub-id pub-id-type="pmid">19966284</pub-id></mixed-citation></ref><ref id="B48"><label>48</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>NC</given-names></name><name><surname>Salazar</surname><given-names>AM</given-names></name><name><surname>Pham</surname><given-names>AH</given-names></name><name><surname>Sweredoski</surname><given-names>MJ</given-names></name><name><surname>Kolawa</surname><given-names>NJ</given-names></name><name><surname>Graham</surname><given-names>RL</given-names></name><etal></etal></person-group><article-title>Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy</article-title>. <source>Hum Mol Genet</source> (<year>2011</year>) <volume>20</volume>:<fpage>1726</fpage>–<lpage>37</lpage><pub-id pub-id-type="doi">10.1093/hmg/ddr048</pub-id><pub-id pub-id-type="pmid">21296869</pub-id></mixed-citation></ref><ref id="B49"><label>49</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gegg</surname><given-names>ME</given-names></name><name><surname>Cooper</surname><given-names>JM</given-names></name><name><surname>Chau</surname><given-names>KY</given-names></name><name><surname>Rojo</surname><given-names>M</given-names></name><name><surname>Schapira</surname><given-names>AH</given-names></name><name><surname>Taanman</surname><given-names>JW</given-names></name></person-group><article-title>Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy</article-title>. <source>Hum Mol Genet</source> (<year>2010</year>) <volume>19</volume>:<fpage>4861</fpage>–<lpage>70</lpage><pub-id pub-id-type="doi">10.1093/hmg/ddq419</pub-id><pub-id pub-id-type="pmid">20871098</pub-id></mixed-citation></ref><ref id="B50"><label>50</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Narendra</surname><given-names>D</given-names></name><name><surname>Tanaka</surname><given-names>A</given-names></name><name><surname>Suen</surname><given-names>DF</given-names></name><name><surname>Youle</surname><given-names>RJ</given-names></name></person-group><article-title>Parkin is recruited selectively to impaired mitochondria and promotes their autophagy</article-title>. <source>J Cell Biol</source> (<year>2008</year>) <volume>183</volume>:<fpage>795</fpage>–<lpage>803</lpage><pub-id pub-id-type="doi">10.1083/jcb.200809125</pub-id><pub-id pub-id-type="pmid">19029340</pub-id></mixed-citation></ref><ref id="B51"><label>51</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Poole</surname><given-names>AC</given-names></name><name><surname>Thomas</surname><given-names>RE</given-names></name><name><surname>Yu</surname><given-names>S</given-names></name><name><surname>Vincow</surname><given-names>ES</given-names></name><name><surname>Pallanck</surname><given-names>L</given-names></name></person-group><article-title>The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway</article-title>. <source>PLoS ONE</source> (<year>2010</year>) <volume>5</volume>:<fpage>e10054</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0010054</pub-id><pub-id pub-id-type="pmid">20383334</pub-id></mixed-citation></ref><ref id="B52"><label>52</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>A</given-names></name><name><surname>Cleland</surname><given-names>MM</given-names></name><name><surname>Xu</surname><given-names>S</given-names></name><name><surname>Narendra</surname><given-names>DP</given-names></name><name><surname>Suen</surname><given-names>DF</given-names></name><name><surname>Karbowski</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin</article-title>. <source>J Cell Biol</source> (<year>2010</year>) <volume>191</volume>:<fpage>1367</fpage>–<lpage>80</lpage><pub-id pub-id-type="doi">10.1083/jcb.201007013</pub-id><pub-id pub-id-type="pmid">21173115</pub-id></mixed-citation></ref><ref id="B53"><label>53</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>X</given-names></name><name><surname>Winter</surname><given-names>D</given-names></name><name><surname>Ashrafi</surname><given-names>G</given-names></name><name><surname>Schlehe</surname><given-names>J</given-names></name><name><surname>Wong</surname><given-names>YL</given-names></name><name><surname>Selkoe</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility</article-title>. <source>Cell</source> (<year>2011</year>) <volume>147</volume>:<fpage>893</fpage>–<lpage>906</lpage><pub-id pub-id-type="doi">10.1016/j.cell.2011.10.018</pub-id><pub-id pub-id-type="pmid">22078885</pub-id></mixed-citation></ref><ref id="B54"><label>54</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yoshii</surname><given-names>SR</given-names></name><name><surname>Kishi</surname><given-names>C</given-names></name><name><surname>Ishihara</surname><given-names>N</given-names></name><name><surname>Mizushima</surname><given-names>N</given-names></name></person-group><article-title>Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane</article-title>. <source>J Biol Chem</source> (<year>2011</year>) <volume>286</volume>:<fpage>19630</fpage>–<lpage>40</lpage><pub-id pub-id-type="doi">10.1074/jbc.M110.209338</pub-id><pub-id pub-id-type="pmid">21454557</pub-id></mixed-citation></ref><ref id="B55"><label>55</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ziviani</surname><given-names>E</given-names></name><name><surname>Tao</surname><given-names>RN</given-names></name><name><surname>Whitworth</surname><given-names>AJ</given-names></name></person-group><article-title><italic>Drosophila</italic> parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2010</year>) <volume>107</volume>:<fpage>5018</fpage>–<lpage>23</lpage><pub-id pub-id-type="doi">10.1073/pnas.0913485107</pub-id><pub-id pub-id-type="pmid">20194754</pub-id></mixed-citation></ref><ref id="B56"><label>56</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>J</given-names></name><name><surname>Ney</surname><given-names>PA</given-names></name></person-group><article-title>Reticulocyte mitophagy: monitoring mitochondrial clearance in a mammalian model</article-title>. <source>Autophagy</source> (<year>2010</year>) <volume>6</volume>:<fpage>405</fpage>–<lpage>8</lpage><pub-id pub-id-type="doi">10.4161/auto.6.3.11245</pub-id><pub-id pub-id-type="pmid">20200480</pub-id></mixed-citation></ref><ref id="B57"><label>57</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Narendra</surname><given-names>D</given-names></name><name><surname>Kane</surname><given-names>LA</given-names></name><name><surname>Hauser DN</surname><given-names>I</given-names></name><name><surname>Fearnley</surname><given-names>M</given-names></name><name><surname>Youle</surname><given-names>RJ</given-names></name></person-group><article-title>p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both</article-title>. <source>Autophagy</source> (<year>2010</year>) <volume>6</volume>:<fpage>1090</fpage>–<lpage>106</lpage><pub-id pub-id-type="doi">10.4161/auto.6.8.13426</pub-id><pub-id pub-id-type="pmid">20890124</pub-id></mixed-citation></ref><ref id="B58"><label>58</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okatsu</surname><given-names>K</given-names></name><name><surname>Saisho</surname><given-names>K</given-names></name><name><surname>Shimanuki</surname><given-names>M</given-names></name><name><surname>Nakada</surname><given-names>K</given-names></name><name><surname>Shitara</surname><given-names>H</given-names></name><name><surname>Sou</surname><given-names>YS</given-names></name><etal></etal></person-group><article-title>p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria</article-title>. <source>Genes Cells</source> (<year>2010</year>) <volume>15</volume>:<fpage>887</fpage>–<lpage>900</lpage><pub-id pub-id-type="doi">10.1111/j.1365-2443.2010.01426.x</pub-id><pub-id pub-id-type="pmid">20604804</pub-id></mixed-citation></ref><ref id="B59"><label>59</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Suen</surname><given-names>DF</given-names></name><name><surname>Narendra</surname><given-names>DP</given-names></name><name><surname>Tanaka</surname><given-names>A</given-names></name><name><surname>Manfredi</surname><given-names>G</given-names></name><name><surname>Youle</surname><given-names>RJ</given-names></name></person-group><article-title>Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2010</year>) <volume>107</volume>:<fpage>11835</fpage>–<lpage>40</lpage><pub-id pub-id-type="doi">10.1073/pnas.0914569107</pub-id><pub-id pub-id-type="pmid">20547844</pub-id></mixed-citation></ref><ref id="B60"><label>60</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ney</surname><given-names>PA</given-names></name></person-group><article-title>Normal and disordered reticulocyte maturation</article-title>. <source>Curr Opin Hematol</source> (<year>2011</year>) <volume>18</volume>:<fpage>152</fpage>–<lpage>7</lpage><pub-id pub-id-type="doi">10.1097/MOH.0b013e328345213e</pub-id><pub-id pub-id-type="pmid">21423015</pub-id></mixed-citation></ref><ref id="B61"><label>61</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Heynen</surname><given-names>MJ</given-names></name><name><surname>Verwilghen</surname><given-names>RL</given-names></name></person-group><article-title>A quantitative ultrastructural study of normal rat erythroblasts and reticulocytes</article-title>. <source>Cell Tissue Res</source> (<year>1982</year>) <volume>224</volume>:<fpage>397</fpage>–<lpage>408</lpage><pub-id pub-id-type="doi">10.1007/BF00216882</pub-id><pub-id pub-id-type="pmid">7105141</pub-id></mixed-citation></ref><ref id="B62"><label>62</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fader</surname><given-names>CM</given-names></name><name><surname>Colombo</surname><given-names>MI</given-names></name></person-group><article-title>Multivesicular bodies and autophagy in erythrocyte maturation</article-title>. <source>Autophagy</source> (<year>2006</year>) <volume>2</volume>:<fpage>122</fpage>–<lpage>5</lpage><pub-id pub-id-type="pmid">16874060</pub-id></mixed-citation></ref><ref id="B63"><label>63</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ding</surname><given-names>WX</given-names></name><name><surname>Ni</surname><given-names>HM</given-names></name><name><surname>Li</surname><given-names>M</given-names></name><name><surname>Liao</surname><given-names>Y</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name><name><surname>Stolz</surname><given-names>DB</given-names></name><etal></etal></person-group><article-title>Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming</article-title>. <source>J Biol Chem</source> (<year>2010</year>) <volume>285</volume>:<fpage>27879</fpage>–<lpage>90</lpage><pub-id pub-id-type="doi">10.1074/jbc.M110.119537</pub-id><pub-id pub-id-type="pmid">20573959</pub-id></mixed-citation></ref><ref id="B64"><label>64</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Novak</surname><given-names>I</given-names></name><name><surname>Kirkin</surname><given-names>V</given-names></name><name><surname>McEwan</surname><given-names>DG</given-names></name><name><surname>Zhang</surname><given-names>J</given-names></name><name><surname>Wild</surname><given-names>P</given-names></name><name><surname>Rozenknop</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Nix is a selective autophagy receptor for mitochondrial clearance</article-title>. <source>EMBO Rep</source> (<year>2010</year>) <volume>11</volume>:<fpage>45</fpage>–<lpage>51</lpage><pub-id pub-id-type="doi">10.1038/embor.2009.256</pub-id><pub-id pub-id-type="pmid">20010802</pub-id></mixed-citation></ref><ref id="B65"><label>65</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>J</given-names></name><name><surname>Randall</surname><given-names>MS</given-names></name><name><surname>Loyd</surname><given-names>MR</given-names></name><name><surname>Dorsey</surname><given-names>FC</given-names></name><name><surname>Kundu</surname><given-names>M</given-names></name><name><surname>Cleveland</surname><given-names>JL</given-names></name><etal></etal></person-group><article-title>Mitochondrial clearance is regulated by Atg7-dependent and -independent mechanisms during reticulocyte maturation</article-title>. <source>Blood</source> (<year>2009</year>) <volume>114</volume>:<fpage>157</fpage>–<lpage>64</lpage><pub-id pub-id-type="doi">10.1182/blood-2008-04-151639</pub-id><pub-id pub-id-type="pmid">19417210</pub-id></mixed-citation></ref><ref id="B66"><label>66</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sandoval</surname><given-names>H</given-names></name><name><surname>Thiagarajan</surname><given-names>P</given-names></name><name><surname>Dasgupta</surname><given-names>SK</given-names></name><name><surname>Schumacher</surname><given-names>A</given-names></name><name><surname>Prchal</surname><given-names>JT</given-names></name><name><surname>Chen</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Essential role for Nix in autophagic maturation of erythroid cells</article-title>. <source>Nature</source> (<year>2008</year>) <volume>454</volume>:<fpage>232</fpage>–<lpage>5</lpage><pub-id pub-id-type="doi">10.1038/nature07006</pub-id><pub-id pub-id-type="pmid">18454133</pub-id></mixed-citation></ref><ref id="B67"><label>67</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schweers</surname><given-names>RL</given-names></name><name><surname>Zhang</surname><given-names>J</given-names></name><name><surname>Randall</surname><given-names>MS</given-names></name><name><surname>Loyd</surname><given-names>MR</given-names></name><name><surname>Li</surname><given-names>W</given-names></name><name><surname>Dorsey</surname><given-names>FC</given-names></name><etal></etal></person-group><article-title>NIX is required for programmed mitochondrial clearance during reticulocyte maturation</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2007</year>) <volume>104</volume>:<fpage>19500</fpage>–<lpage>5</lpage><pub-id pub-id-type="doi">10.1073/pnas.0708818104</pub-id><pub-id pub-id-type="pmid">18048346</pub-id></mixed-citation></ref><ref id="B68"><label>68</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mortensen</surname><given-names>M</given-names></name><name><surname>Ferguson</surname><given-names>DJ</given-names></name><name><surname>Edelmann</surname><given-names>M</given-names></name><name><surname>Kessler</surname><given-names>B</given-names></name><name><surname>Morten</surname><given-names>KJ</given-names></name><name><surname>Komatsu</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo</article-title>. <source>Proc Natl Acad Sci USA</source> (<year>2010</year>) <volume>107</volume>:<fpage>832</fpage>–<lpage>7</lpage><pub-id pub-id-type="doi">10.1073/pnas.0913170107</pub-id><pub-id pub-id-type="pmid">20080761</pub-id></mixed-citation></ref><ref id="B69"><label>69</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dumollard</surname><given-names>R</given-names></name><name><surname>Duchen</surname><given-names>M</given-names></name><name><surname>Carroll</surname><given-names>J</given-names></name></person-group><article-title>The role of mitochondrial function in the oocyte and embryo</article-title>. <source>Curr Top Dev Biol</source> (<year>2007</year>) <volume>77</volume>:<fpage>21</fpage>–<lpage>49</lpage><pub-id pub-id-type="doi">10.1016/S0070-2153(06)77002-8</pub-id><pub-id pub-id-type="pmid">17222699</pub-id></mixed-citation></ref><ref id="B70"><label>70</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al Rawi</surname><given-names>S</given-names></name><name><surname>Louvet-Vallee</surname><given-names>S</given-names></name><name><surname>Djeddi</surname><given-names>A</given-names></name><name><surname>Sachse</surname><given-names>M</given-names></name><name><surname>Culetto</surname><given-names>E</given-names></name><name><surname>Hajjar</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission</article-title>. <source>Science</source> (<year>2011</year>) <volume>334</volume>:<fpage>1144</fpage>–<lpage>7</lpage><pub-id pub-id-type="doi">10.1126/science.1211878</pub-id><pub-id pub-id-type="pmid">22033522</pub-id></mixed-citation></ref><ref id="B71"><label>71</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cummins</surname><given-names>JM</given-names></name></person-group><article-title>Fertilization and elimination of the paternal mitochondrial genome</article-title>. <source>Hum Reprod</source> (<year>2000</year>) <volume>15</volume>(<issue>Suppl 2</issue>):<fpage>92</fpage>–<lpage>101</lpage><pub-id pub-id-type="doi">10.1093/humrep/15.suppl_2.92</pub-id><pub-id pub-id-type="pmid">11041517</pub-id></mixed-citation></ref><ref id="B72"><label>72</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sato</surname><given-names>M</given-names></name><name><surname>Sato</surname><given-names>K</given-names></name></person-group><article-title>Degradation of paternal mitochondria by fertilization-triggered autophagy in <italic>C. elegans</italic> embryos</article-title>. <source>Science</source> (<year>2011</year>) <volume>334</volume>:<fpage>1141</fpage>–<lpage>4</lpage><pub-id pub-id-type="doi">10.1126/science.1210333</pub-id><pub-id pub-id-type="pmid">21998252</pub-id></mixed-citation></ref><ref id="B73"><label>73</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Clark</surname><given-names>IE</given-names></name><name><surname>Dodson</surname><given-names>MW</given-names></name><name><surname>Jiang</surname><given-names>C</given-names></name><name><surname>Cao</surname><given-names>JH</given-names></name><name><surname>Huh</surname><given-names>JR</given-names></name><name><surname>Seol</surname><given-names>JH</given-names></name><etal></etal></person-group><article-title>Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin</article-title>. <source>Nature</source> (<year>2006</year>) <volume>441</volume>:<fpage>1162</fpage>–<lpage>6</lpage><pub-id pub-id-type="doi">10.1038/nature04779</pub-id><pub-id pub-id-type="pmid">16672981</pub-id></mixed-citation></ref><ref id="B74"><label>74</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Greene</surname><given-names>JC</given-names></name><name><surname>Whitworth</surname><given-names>AJ</given-names></name><name><surname>Kuo</surname><given-names>I</given-names></name><name><surname>Andrews</surname><given-names>LA</given-names></name><name><surname>Feany</surname><given-names>MB</given-names></name><name><surname>Pallanck</surname><given-names>LJ</given-names></name></person-group><article-title>Mitochondrial pathology and apoptotic muscle degeneration in <italic>Drosophila</italic> parkin mutants</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2003</year>) <volume>100</volume>:<fpage>4078</fpage>–<lpage>83</lpage><pub-id pub-id-type="doi">10.1073/pnas.0737556100</pub-id><pub-id pub-id-type="pmid">12642658</pub-id></mixed-citation></ref><ref id="B75"><label>75</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Park</surname><given-names>J</given-names></name><name><surname>Lee</surname><given-names>SB</given-names></name><name><surname>Lee</surname><given-names>S</given-names></name><name><surname>Kim</surname><given-names>Y</given-names></name><name><surname>Song</surname><given-names>S</given-names></name><name><surname>Kim</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Mitochondrial dysfunction in <italic>Drosophila</italic> PINK1 mutants is complemented by parkin</article-title>. <source>Nature</source> (<year>2006</year>) <volume>441</volume>:<fpage>1157</fpage>–<lpage>61</lpage><pub-id pub-id-type="doi">10.1038/nature04788</pub-id><pub-id pub-id-type="pmid">16672980</pub-id></mixed-citation></ref><ref id="B76"><label>76</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cai</surname><given-names>Q</given-names></name><name><surname>Zakaria</surname><given-names>HM</given-names></name><name><surname>Simone</surname><given-names>A</given-names></name><name><surname>Sheng</surname><given-names>ZH</given-names></name></person-group><article-title>Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons</article-title>. <source>Curr Biol</source> (<year>2012</year>) <volume>22</volume>:<fpage>545</fpage>–<lpage>52</lpage><pub-id pub-id-type="doi">10.1016/j.cub.2012.02.005</pub-id><pub-id pub-id-type="pmid">22342752</pub-id></mixed-citation></ref><ref id="B77"><label>77</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Joselin</surname><given-names>AP</given-names></name><name><surname>Hewitt</surname><given-names>SJ</given-names></name><name><surname>Callaghan</surname><given-names>SM</given-names></name><name><surname>Kim</surname><given-names>RH</given-names></name><name><surname>Chung</surname><given-names>YH</given-names></name><name><surname>Mak</surname><given-names>TW</given-names></name><etal></etal></person-group><article-title>ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons</article-title>. <source>Hum Mol Genet</source> (<year>2012</year>) <volume>21</volume>:<fpage>4888</fpage>–<lpage>903</lpage><pub-id pub-id-type="doi">10.1093/hmg/dds325</pub-id><pub-id pub-id-type="pmid">22872702</pub-id></mixed-citation></ref><ref id="B78"><label>78</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seibler</surname><given-names>P</given-names></name><name><surname>Graziotto</surname><given-names>J</given-names></name><name><surname>Jeong</surname><given-names>H</given-names></name><name><surname>Simunovic</surname><given-names>F</given-names></name><name><surname>Klein</surname><given-names>C</given-names></name><name><surname>Krainc</surname><given-names>D</given-names></name></person-group><article-title>Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells</article-title>. <source>J Neurosci</source> (<year>2011</year>) <volume>31</volume>:<fpage>5970</fpage>–<lpage>6</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.4441-10.2011</pub-id><pub-id pub-id-type="pmid">21508222</pub-id></mixed-citation></ref><ref id="B79"><label>79</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Laar</surname><given-names>VS</given-names></name><name><surname>Arnold</surname><given-names>B</given-names></name><name><surname>Cassady</surname><given-names>SJ</given-names></name><name><surname>Chu</surname><given-names>CT</given-names></name><name><surname>Burton</surname><given-names>EA</given-names></name><name><surname>Berman</surname><given-names>SB</given-names></name></person-group><article-title>Bioenergetics of neurons inhibit the translocation response of Parkin following rapid mitochondrial depolarization</article-title>. <source>Hum Mol Genet</source> (<year>2011</year>) <volume>20</volume>:<fpage>927</fpage>–<lpage>40</lpage><pub-id pub-id-type="doi">10.1093/hmg/ddq531</pub-id><pub-id pub-id-type="pmid">21147754</pub-id></mixed-citation></ref><ref id="B80"><label>80</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rakovic</surname><given-names>A</given-names></name><name><surname>Shurkewitsch</surname><given-names>K</given-names></name><name><surname>Seibler</surname><given-names>P</given-names></name><name><surname>Grunewald</surname><given-names>A</given-names></name><name><surname>Zanon</surname><given-names>A</given-names></name><name><surname>Hagenah</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons</article-title>. <source>J Biol Chem</source> (<year>2013</year>) <volume>288</volume>:<fpage>2223</fpage>–<lpage>37</lpage><pub-id pub-id-type="doi">10.1074/jbc.M112.391680</pub-id><pub-id pub-id-type="pmid">23212910</pub-id></mixed-citation></ref><ref id="B81"><label>81</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Almeida</surname><given-names>A</given-names></name><name><surname>Almeida</surname><given-names>J</given-names></name><name><surname>Bolanos</surname><given-names>JP</given-names></name><name><surname>Moncada</surname><given-names>S</given-names></name></person-group><article-title>Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2001</year>) <volume>98</volume>:<fpage>15294</fpage>–<lpage>9</lpage><pub-id pub-id-type="doi">10.1073/pnas.261560998</pub-id><pub-id pub-id-type="pmid">11742096</pub-id></mixed-citation></ref><ref id="B82"><label>82</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Almeida</surname><given-names>A</given-names></name><name><surname>Moncada</surname><given-names>S</given-names></name><name><surname>Bolanos</surname><given-names>JP</given-names></name></person-group><article-title>Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway</article-title>. <source>Nat Cell Biol</source> (<year>2004</year>) <volume>6</volume>:<fpage>45</fpage>–<lpage>51</lpage><pub-id pub-id-type="doi">10.1038/ncb1080</pub-id><pub-id pub-id-type="pmid">14688792</pub-id></mixed-citation></ref><ref id="B83"><label>83</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bolanos</surname><given-names>JP</given-names></name><name><surname>Almeida</surname><given-names>A</given-names></name><name><surname>Moncada</surname><given-names>S</given-names></name></person-group><article-title>Glycolysis: a bioenergetic or a survival pathway?</article-title><source>Trends Biochem Sci</source> (<year>2010</year>) <volume>35</volume>:<fpage>145</fpage>–<lpage>9</lpage><pub-id pub-id-type="doi">10.1016/j.tibs.2009.10.006</pub-id><pub-id pub-id-type="pmid">20006513</pub-id></mixed-citation></ref><ref id="B84"><label>84</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Herrero-Mendez</surname><given-names>A</given-names></name><name><surname>Almeida</surname><given-names>A</given-names></name><name><surname>Fernandez</surname><given-names>E</given-names></name><name><surname>Maestre</surname><given-names>C</given-names></name><name><surname>Moncada</surname><given-names>S</given-names></name><name><surname>Bolanos</surname><given-names>JP</given-names></name></person-group><article-title>The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1</article-title>. <source>Nat Cell Biol</source> (<year>2009</year>) <volume>11</volume>:<fpage>747</fpage>–<lpage>52</lpage><pub-id pub-id-type="doi">10.1038/ncb1881</pub-id><pub-id pub-id-type="pmid">19448625</pub-id></mixed-citation></ref><ref id="B85"><label>85</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ekstrand</surname><given-names>MI</given-names></name><name><surname>Terzioglu</surname><given-names>M</given-names></name><name><surname>Galter</surname><given-names>D</given-names></name><name><surname>Zhu</surname><given-names>S</given-names></name><name><surname>Hofstetter</surname><given-names>C</given-names></name><name><surname>Lindqvist</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2007</year>) <volume>104</volume>:<fpage>1325</fpage>–<lpage>30</lpage><pub-id pub-id-type="doi">10.1073/pnas.0605208103</pub-id><pub-id pub-id-type="pmid">17227870</pub-id></mixed-citation></ref><ref id="B86"><label>86</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sterky</surname><given-names>FH</given-names></name><name><surname>Lee</surname><given-names>S</given-names></name><name><surname>Wibom</surname><given-names>R</given-names></name><name><surname>Olson</surname><given-names>L</given-names></name><name><surname>Larsson</surname><given-names>NG</given-names></name></person-group><article-title>Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo</article-title>. <source>Proc Natl Acad Sci USA</source> (<year>2011</year>) <volume>108</volume>:<fpage>12937</fpage>–<lpage>42</lpage><pub-id pub-id-type="doi">10.1073/pnas.1103295108</pub-id><pub-id pub-id-type="pmid">21768369</pub-id></mixed-citation></ref><ref id="B87"><label>87</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vincow</surname><given-names>ES</given-names></name><name><surname>Merrihew</surname><given-names>G</given-names></name><name><surname>Thomas</surname><given-names>RE</given-names></name><name><surname>Shulman</surname><given-names>NJ</given-names></name><name><surname>Beyer</surname><given-names>RP</given-names></name><name><surname>Maccoss</surname><given-names>MJ</given-names></name><etal></etal></person-group><article-title>The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo</article-title>. <source>Proc Natl Acad Sci U S A</source> (<year>2013</year>) <volume>110</volume>:<fpage>6400</fpage>–<lpage>5</lpage><pub-id pub-id-type="doi">10.1073/pnas.1221132110</pub-id><pub-id pub-id-type="pmid">23509287</pub-id></mixed-citation></ref><ref id="B88"><label>88</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>JY</given-names></name><name><surname>Nagano</surname><given-names>Y</given-names></name><name><surname>Taylor</surname><given-names>JP</given-names></name><name><surname>Lim</surname><given-names>KL</given-names></name><name><surname>Yao</surname><given-names>TP</given-names></name></person-group><article-title>Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy</article-title>. <source>J Cell Biol</source> (<year>2010</year>) <volume>189</volume>:<fpage>671</fpage>–<lpage>9</lpage><pub-id pub-id-type="doi">10.1083/jcb.201001039</pub-id><pub-id pub-id-type="pmid">20457763</pub-id></mixed-citation></ref><ref id="B89"><label>89</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>Y</given-names></name><name><surname>Vashisht</surname><given-names>AA</given-names></name><name><surname>Tchieu</surname><given-names>J</given-names></name><name><surname>Wohlschlegel</surname><given-names>JA</given-names></name><name><surname>Dreier</surname><given-names>L</given-names></name></person-group><article-title>Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy</article-title>. <source>J Biol Chem</source> (<year>2012</year>) <volume>287</volume>:<fpage>40652</fpage>–<lpage>60</lpage><pub-id pub-id-type="doi">10.1074/jbc.M112.419721</pub-id><pub-id pub-id-type="pmid">23060438</pub-id></mixed-citation></ref><ref id="B90"><label>90</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Humbeeck</surname><given-names>C</given-names></name><name><surname>Cornelissen</surname><given-names>T</given-names></name><name><surname>Hofkens</surname><given-names>H</given-names></name><name><surname>Mandemakers</surname><given-names>W</given-names></name><name><surname>Gevaert</surname><given-names>K</given-names></name><name><surname>De Strooper</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Parkin interacts with Ambra1 to induce mitophagy</article-title>. <source>J Neurosci</source> (<year>2011</year>) <volume>31</volume>:<fpage>10249</fpage>–<lpage>61</lpage><pub-id pub-id-type="doi">10.1523/JNEUROSCI.1917-11.2011</pub-id><pub-id pub-id-type="pmid">21753002</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C27 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000C27 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.29. |  |