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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin</title><author><name sortKey="Durcan, Thomas M" sort="Durcan, Thomas M" uniqKey="Durcan T" first="Thomas M" last="Durcan">Thomas M. Durcan</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tang, Matthew Y" sort="Tang, Matthew Y" uniqKey="Tang M" first="Matthew Y" last="Tang">Matthew Y. Tang</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Perusse, Joelle R" sort="Perusse, Joelle R" uniqKey="Perusse J" first="Joëlle R" last="Pérusse">Joëlle R. Pérusse</name><affiliation><nlm:aff id="au2"><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dashti, Eman A" sort="Dashti, Eman A" uniqKey="Dashti E" first="Eman A" last="Dashti">Eman A. Dashti</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Aguileta, Miguel A" sort="Aguileta, Miguel A" uniqKey="Aguileta M" first="Miguel A" last="Aguileta">Miguel A. Aguileta</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></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="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gros, Priti" sort="Gros, Priti" uniqKey="Gros P" first="Priti" last="Gros">Priti Gros</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shaler, Thomas A" sort="Shaler, Thomas A" uniqKey="Shaler T" first="Thomas A" last="Shaler">Thomas A. Shaler</name><affiliation><nlm:aff id="au3"><institution>Physics Laboratory, SRI International</institution><addr-line>Menlo Park, CA, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Faubert, Denis" sort="Faubert, Denis" uniqKey="Faubert D" first="Denis" last="Faubert">Denis Faubert</name><affiliation><nlm:aff id="au2"><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Coulombe, Benoit" sort="Coulombe, Benoit" uniqKey="Coulombe B" first="Benoit" last="Coulombe">Benoit Coulombe</name><affiliation><nlm:aff id="au2"><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au4"><institution>Department of Biochemistry, Université de Montréal</institution><addr-line>Montréal, QC, Canada</addr-line></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="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25216678</idno><idno type="pmc">4283406</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283406</idno><idno type="RBID">PMC:4283406</idno><idno type="doi">10.15252/embj.201489729</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000532</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000532</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin</title><author><name sortKey="Durcan, Thomas M" sort="Durcan, Thomas M" uniqKey="Durcan T" first="Thomas M" last="Durcan">Thomas M. Durcan</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Tang, Matthew Y" sort="Tang, Matthew Y" uniqKey="Tang M" first="Matthew Y" last="Tang">Matthew Y. Tang</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Perusse, Joelle R" sort="Perusse, Joelle R" uniqKey="Perusse J" first="Joëlle R" last="Pérusse">Joëlle R. Pérusse</name><affiliation><nlm:aff id="au2"><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Dashti, Eman A" sort="Dashti, Eman A" uniqKey="Dashti E" first="Eman A" last="Dashti">Eman A. Dashti</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Aguileta, Miguel A" sort="Aguileta, Miguel A" uniqKey="Aguileta M" first="Miguel A" last="Aguileta">Miguel A. Aguileta</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></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="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gros, Priti" sort="Gros, Priti" uniqKey="Gros P" first="Priti" last="Gros">Priti Gros</name><affiliation><nlm:aff id="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shaler, Thomas A" sort="Shaler, Thomas A" uniqKey="Shaler T" first="Thomas A" last="Shaler">Thomas A. Shaler</name><affiliation><nlm:aff id="au3"><institution>Physics Laboratory, SRI International</institution><addr-line>Menlo Park, CA, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Faubert, Denis" sort="Faubert, Denis" uniqKey="Faubert D" first="Denis" last="Faubert">Denis Faubert</name><affiliation><nlm:aff id="au2"><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author><author><name sortKey="Coulombe, Benoit" sort="Coulombe, Benoit" uniqKey="Coulombe B" first="Benoit" last="Coulombe">Benoit Coulombe</name><affiliation><nlm:aff id="au2"><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au4"><institution>Department of Biochemistry, Université de Montréal</institution><addr-line>Montréal, QC, Canada</addr-line></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="au1"><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">The EMBO Journal</title><idno type="ISSN">0261-4189</idno><idno type="eISSN">1460-2075</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mutations in the <italic>Park2</italic> gene, encoding the E3 ubiquitin-ligase parkin, are responsible for a familial form of Parkinson's disease (PD). Parkin-mediated ubiquitination is critical for the efficient elimination of depolarized dysfunctional mitochondria by autophagy (mitophagy). As damaged mitochondria are a major source of toxic reactive oxygen species within the cell, this pathway is believed to be highly relevant to the pathogenesis of PD. Little is known about how parkin-mediated ubiquitination is regulated during mitophagy or about the nature of the ubiquitin conjugates involved. We report here that USP8/UBPY, a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for parkin-mediated mitophagy. USP8 preferentially removes non-canonical K6-linked ubiquitin chains from parkin, a process required for the efficient recruitment of parkin to depolarized mitochondria and for their subsequent elimination by mitophagy. This work uncovers a novel role for USP8-mediated deubiquitination of K6-linked ubiquitin conjugates from parkin in mitochondrial quality control.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">EMBO J</journal-id><journal-id journal-id-type="iso-abbrev">EMBO J</journal-id><journal-id journal-id-type="publisher-id">embj</journal-id><journal-title-group><journal-title>The EMBO Journal</journal-title></journal-title-group><issn pub-type="ppub">0261-4189</issn><issn pub-type="epub">1460-2075</issn><publisher><publisher-name>BlackWell Publishing Ltd</publisher-name><publisher-loc>Oxford, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25216678</article-id><article-id pub-id-type="pmc">4283406</article-id><article-id pub-id-type="doi">10.15252/embj.201489729</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Durcan</surname><given-names>Thomas M</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Tang</surname><given-names>Matthew Y</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Pérusse</surname><given-names>Joëlle R</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dashti</surname><given-names>Eman A</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Aguileta</surname><given-names>Miguel A</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>McLelland</surname><given-names>Gian-Luca</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gros</surname><given-names>Priti</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Shaler</surname><given-names>Thomas A</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Faubert</surname><given-names>Denis</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Coulombe</surname><given-names>Benoit</given-names></name><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Fon</surname><given-names>Edward A</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><aff id="au1"><label>1</label><institution>McGill Parkinson Program, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University</institution><addr-line>Montréal, QC, Canada</addr-line></aff><aff id="au2"><label>2</label><institution>Institut de Recherches Cliniques de Montréal (IRCM)</institution><addr-line>Montréal, QC, Canada</addr-line></aff><aff id="au3"><label>3</label><institution>Physics Laboratory, SRI International</institution><addr-line>Menlo Park, CA, USA</addr-line></aff><aff id="au4"><label>4</label><institution>Department of Biochemistry, Université de Montréal</institution><addr-line>Montréal, QC, Canada</addr-line></aff></contrib-group><author-notes><corresp id="cor1">*Corresponding author. Tel: +1 514 398 8398; Fax: +1 514 398 5214; E-mail: <email>ted.fon@mcgill.ca</email></corresp><fn><p><bold>Subject Categories</bold> Post-translational Modifications, Proteolysis & Proteomics; Membrane & Intracellular Transport; Neuroscience</p></fn></author-notes><pub-date pub-type="ppub"><day>03</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>12</day><month>9</month><year>2014</year></pub-date><volume>33</volume><issue>21</issue><fpage>2473</fpage><lpage>2491</lpage><history><date date-type="received"><day>06</day><month>8</month><year>2014</year></date><date date-type="rev-recd"><day>20</day><month>8</month><year>2014</year></date><date date-type="accepted"><day>21</day><month>8</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 The Authors</copyright-statement><copyright-year>2014</copyright-year></permissions><related-article related-article-type="companion" id="d35e208" vol="33" page="2442" issue="21" xlink:href="25274967" ext-link-type="pubmed"></related-article><abstract><p>Mutations in the <italic>Park2</italic> gene, encoding the E3 ubiquitin-ligase parkin, are responsible for a familial form of Parkinson's disease (PD). Parkin-mediated ubiquitination is critical for the efficient elimination of depolarized dysfunctional mitochondria by autophagy (mitophagy). As damaged mitochondria are a major source of toxic reactive oxygen species within the cell, this pathway is believed to be highly relevant to the pathogenesis of PD. Little is known about how parkin-mediated ubiquitination is regulated during mitophagy or about the nature of the ubiquitin conjugates involved. We report here that USP8/UBPY, a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for parkin-mediated mitophagy. USP8 preferentially removes non-canonical K6-linked ubiquitin chains from parkin, a process required for the efficient recruitment of parkin to depolarized mitochondria and for their subsequent elimination by mitophagy. This work uncovers a novel role for USP8-mediated deubiquitination of K6-linked ubiquitin conjugates from parkin in mitochondrial quality control.</p></abstract><kwd-group><kwd>deubiquitination</kwd><kwd>mitophagy</kwd><kwd>parkin</kwd><kwd>ubiquitin</kwd><kwd>USP8</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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