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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">BAG2 Gene-mediated Regulation of PINK1 Protein Is Critical for Mitochondrial Translocation of PARKIN and Neuronal Survival<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Qu, Dianbo" sort="Qu, Dianbo" uniqKey="Qu D" first="Dianbo" last="Qu">Dianbo Qu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Hage, Ali" sort="Hage, Ali" uniqKey="Hage A" first="Ali" last="Hage">Ali Hage</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Don Carolis, Katie" sort="Don Carolis, Katie" uniqKey="Don Carolis K" first="Katie" last="Don-Carolis">Katie Don-Carolis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Huang, En" sort="Huang, En" uniqKey="Huang E" first="En" last="Huang">En Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Joselin, Alvin" sort="Joselin, Alvin" uniqKey="Joselin A" first="Alvin" last="Joselin">Alvin Joselin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Safarpour, Farzaneh" sort="Safarpour, Farzaneh" uniqKey="Safarpour F" first="Farzaneh" last="Safarpour">Farzaneh Safarpour</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Marcogliese, Paul C" sort="Marcogliese, Paul C" uniqKey="Marcogliese P" first="Paul C." last="Marcogliese">Paul C. Marcogliese</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Rousseaux, Maxime W C" sort="Rousseaux, Maxime W C" uniqKey="Rousseaux M" first="Maxime W. C." last="Rousseaux">Maxime W. C. Rousseaux</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Sarah J" sort="Hewitt, Sarah J" uniqKey="Hewitt S" first="Sarah J." last="Hewitt">Sarah J. Hewitt</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Huang, Tianwen" sort="Huang, Tianwen" uniqKey="Huang T" first="Tianwen" last="Huang">Tianwen Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Im, Doo Soon" sort="Im, Doo Soon" uniqKey="Im D" first="Doo-Soon" last="Im">Doo-Soon Im</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Callaghan, Steve" sort="Callaghan, Steve" uniqKey="Callaghan S" first="Steve" last="Callaghan">Steve Callaghan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Dewar Darch, Danielle" sort="Dewar Darch, Danielle" uniqKey="Dewar Darch D" first="Danielle" last="Dewar-Darch">Danielle Dewar-Darch</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Ottawa Institute of Systems Biology, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Figeys, Daniel" sort="Figeys, Daniel" uniqKey="Figeys D" first="Daniel" last="Figeys">Daniel Figeys</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Ottawa Institute of Systems Biology, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26538564</idno><idno type="pmc">4683266</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683266</idno><idno type="RBID">PMC:4683266</idno><idno type="doi">10.1074/jbc.M115.677815</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000039</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000039</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">BAG2 Gene-mediated Regulation of PINK1 Protein Is Critical for Mitochondrial Translocation of PARKIN and Neuronal Survival<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Qu, Dianbo" sort="Qu, Dianbo" uniqKey="Qu D" first="Dianbo" last="Qu">Dianbo Qu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Hage, Ali" sort="Hage, Ali" uniqKey="Hage A" first="Ali" last="Hage">Ali Hage</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Don Carolis, Katie" sort="Don Carolis, Katie" uniqKey="Don Carolis K" first="Katie" last="Don-Carolis">Katie Don-Carolis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Huang, En" sort="Huang, En" uniqKey="Huang E" first="En" last="Huang">En Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Joselin, Alvin" sort="Joselin, Alvin" uniqKey="Joselin A" first="Alvin" last="Joselin">Alvin Joselin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Safarpour, Farzaneh" sort="Safarpour, Farzaneh" uniqKey="Safarpour F" first="Farzaneh" last="Safarpour">Farzaneh Safarpour</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Marcogliese, Paul C" sort="Marcogliese, Paul C" uniqKey="Marcogliese P" first="Paul C." last="Marcogliese">Paul C. Marcogliese</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Rousseaux, Maxime W C" sort="Rousseaux, Maxime W C" uniqKey="Rousseaux M" first="Maxime W. C." last="Rousseaux">Maxime W. C. Rousseaux</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Hewitt, Sarah J" sort="Hewitt, Sarah J" uniqKey="Hewitt S" first="Sarah J." last="Hewitt">Sarah J. Hewitt</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Huang, Tianwen" sort="Huang, Tianwen" uniqKey="Huang T" first="Tianwen" last="Huang">Tianwen Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Im, Doo Soon" sort="Im, Doo Soon" uniqKey="Im D" first="Doo-Soon" last="Im">Doo-Soon Im</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Callaghan, Steve" sort="Callaghan, Steve" uniqKey="Callaghan S" first="Steve" last="Callaghan">Steve Callaghan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Dewar Darch, Danielle" sort="Dewar Darch, Danielle" uniqKey="Dewar Darch D" first="Danielle" last="Dewar-Darch">Danielle Dewar-Darch</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Ottawa Institute of Systems Biology, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Figeys, Daniel" sort="Figeys, Daniel" uniqKey="Figeys D" first="Daniel" last="Figeys">Daniel Figeys</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Ottawa Institute of Systems Biology, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author><author><name sortKey="Park, David S" sort="Park, David S" uniqKey="Park D" first="David S." last="Park">David S. Park</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Brain and Mind Research Institute</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Emerging evidence has demonstrated a growing genetic component in Parkinson disease (PD). For instance, loss-of-function mutations in <italic>PINK1</italic> or <italic>PARKIN</italic> can cause autosomal recessive PD. Recently, PINK1 and PARKIN have been implicated in the same signaling pathway to regulate mitochondrial clearance through recruitment of PARKIN by stabilization of PINK1 on the outer membrane of depolarized mitochondria. The precise mechanisms that govern this process remain enigmatic. In this study, we identify Bcl2-associated athanogene 2 (BAG2) as a factor that promotes mitophagy. BAG2 inhibits PINK1 degradation by blocking the ubiquitination pathway. Stabilization of PINK1 by BAG2 triggers PARKIN-mediated mitophagy and protects neurons against 1-methyl-4-phenylpyridinium-induced oxidative stress in an <italic>in vitro</italic> cell model of PD. Collectively, our findings support the notion that BAG2 is an upstream regulator of the PINK1/PARKIN signaling pathway.</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">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>11200 Rockville Pike, Suite 302, Rockville, MD 20852-3110, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26538564</article-id><article-id pub-id-type="pmc">4683266</article-id><article-id pub-id-type="publisher-id">M115.677815</article-id><article-id pub-id-type="doi">10.1074/jbc.M115.677815</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neurobiology</subject></subj-group></article-categories><title-group><article-title>BAG2 Gene-mediated Regulation of PINK1 Protein Is Critical for Mitochondrial Translocation of PARKIN and Neuronal Survival<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">BAG2 Stabilizes PINK1 to Allow Translocation of PARKIN</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Qu</surname><given-names>Dianbo</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hage</surname><given-names>Ali</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Don-Carolis</surname><given-names>Katie</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>En</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Joselin</surname><given-names>Alvin</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Safarpour</surname><given-names>Farzaneh</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Marcogliese</surname><given-names>Paul C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rousseaux</surname><given-names>Maxime W. C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hewitt</surname><given-names>Sarah J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Tianwen</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Im</surname><given-names>Doo-Soon</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Callaghan</surname><given-names>Steve</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dewar-Darch</surname><given-names>Danielle</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Figeys</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Slack</surname><given-names>Ruth S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>David S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Department of Cellular and Molecular Medicine,</aff><aff id="aff2"><label>§</label>Brain and Mind Research Institute, and</aff><aff id="aff3"><label>¶</label>Ottawa Institute of Systems Biology, University of Ottawa, Ottawa K1H 8M5, Ontario, Canada</aff></contrib-group><author-notes><corresp id="cor1"><label>1</label> To whom correspondence should be addressed: <addr-line>Dept. of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, ON, Canada.</addr-line> Tel.: <phone>613-562-5800, ext. 8816</phone>; Fax: <fax>613-864-8816</fax>; E-mail: <email>dpark@uottawa.ca</email>.</corresp></author-notes><pub-date pub-type="ppub"><day>18</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>4</day><month>11</month><year>2015</year></pub-date><volume>290</volume><issue>51</issue><fpage>30441</fpage><lpage>30452</lpage><history><date date-type="received"><day>9</day><month>7</month><year>2015</year></date><date date-type="rev-recd"><day>3</day><month>11</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>The American Society for Biochemistry and Molecular Biology, Inc.</copyright-holder></permissions><self-uri content-type="pdf" xlink:href="zbc05115030441.pdf"></self-uri><abstract><p>Emerging evidence has demonstrated a growing genetic component in Parkinson disease (PD). For instance, loss-of-function mutations in <italic>PINK1</italic> or <italic>PARKIN</italic> can cause autosomal recessive PD. Recently, PINK1 and PARKIN have been implicated in the same signaling pathway to regulate mitochondrial clearance through recruitment of PARKIN by stabilization of PINK1 on the outer membrane of depolarized mitochondria. The precise mechanisms that govern this process remain enigmatic. In this study, we identify Bcl2-associated athanogene 2 (BAG2) as a factor that promotes mitophagy. BAG2 inhibits PINK1 degradation by blocking the ubiquitination pathway. Stabilization of PINK1 by BAG2 triggers PARKIN-mediated mitophagy and protects neurons against 1-methyl-4-phenylpyridinium-induced oxidative stress in an <italic>in vitro</italic> cell model of PD. Collectively, our findings support the notion that BAG2 is an upstream regulator of the PINK1/PARKIN signaling pathway.</p></abstract><kwd-group><kwd>cell death</kwd><kwd>neurodegenerative disease</kwd><kwd>Parkinson disease</kwd><kwd>translocation</kwd><kwd>ubiquitylation (ubiquitination)</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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