USP8 and PARK2/parkin-mediated mitophagy
Identifieur interne : 000026 ( Pmc/Curation ); précédent : 000025; suivant : 000027USP8 and PARK2/parkin-mediated mitophagy
Auteurs : Thomas M. Durcan ; Edward A. FonSource :
- Autophagy [ 1554-8627 ] ; 2015.
Abstract
The Parkinson disease (PD)-associated E3-ubiquitin (Ub) ligase PARK2/parkin plays a central role in many stress response pathways, and in particular, in mitochondrial quality control. Within this pathway, PARK2 activation is accompanied by a robust increase in its autoubiquitination, followed by clearance of the damaged mitochondria by selective autophagy (mitophagy). Yet, little is known about how this auto-ubiquitination is regulated during mitophagy. In our study, we demonstrate that PARK2 forms predominantly K6-linked Ub conjugates on itself. Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway. When USP8 is silenced, a persistence of K6-linked Ub conjugates on PARK2 delays both its translocation to damaged mitochondria and successful completion of mitophagy. Taken together, these findings implicate a novel role for K6-linked Ub conjugates and USP8-mediated deubiquitination in the regulation of PARK2 in mitochondrial quality control.
Url:
DOI: 10.1080/15548627.2015.1009794
PubMed: 25700639
PubMed Central: 4502724
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">USP8 and PARK2/parkin-mediated mitophagy </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>NONE</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>NONE</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25700639</idno><idno type="pmc">4502724</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502724</idno><idno type="RBID">PMC:4502724</idno><idno type="doi">10.1080/15548627.2015.1009794</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000026</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000026</idno><idno type="wicri:Area/Pmc/Curation">000026</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000026</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">USP8 and PARK2/parkin-mediated mitophagy </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>NONE</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>NONE</nlm:aff></affiliation></author></analytic><series><title level="j">Autophagy</title><idno type="ISSN">1554-8627</idno><idno type="eISSN">1554-8635</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>The Parkinson disease (PD)-associated E3-ubiquitin (Ub) ligase PARK2/parkin plays a central role in many stress response pathways, and in particular, in mitochondrial quality control. Within this pathway, PARK2 activation is accompanied by a robust increase in its autoubiquitination, followed by clearance of the damaged mitochondria by selective autophagy (mitophagy). Yet, little is known about how this auto-ubiquitination is regulated during mitophagy. In our study, we demonstrate that PARK2 forms predominantly K6-linked Ub conjugates on itself. Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway. When USP8 is silenced, a persistence of K6-linked Ub conjugates on PARK2 delays both its translocation to damaged mitochondria and successful completion of mitophagy. Taken together, these findings implicate a novel role for K6-linked Ub conjugates and USP8-mediated deubiquitination in the regulation of PARK2 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">Autophagy</journal-id><journal-id journal-id-type="iso-abbrev">Autophagy</journal-id><journal-id journal-id-type="pmc">KAUP</journal-id><journal-title-group><journal-title>Autophagy</journal-title></journal-title-group><issn pub-type="ppub">1554-8627</issn><issn pub-type="epub">1554-8635</issn><publisher><publisher-name>Taylor & Francis</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25700639</article-id><article-id pub-id-type="pmc">4502724</article-id><article-id pub-id-type="publisher-id">1009794</article-id><article-id pub-id-type="doi">10.1080/15548627.2015.1009794</article-id><article-categories><subj-group subj-group-type="heading"><subject>Autophagic Puncta</subject></subj-group></article-categories><title-group><article-title>USP8 and PARK2/parkin-mediated mitophagy </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="af0001"><sup>1</sup></xref><xref ref-type="corresp" rid="an0001"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fon</surname><given-names>Edward A</given-names></name><xref ref-type="aff" rid="af0001"><sup>1</sup></xref></contrib><aff id="af0001"><label>01</label><institution>McGill Parkinson's Program; Department of Neurology and Neurosurgery</institution>;<institution>Montreal Neurological Institute; McGill University</institution>; Montreal,<country>Canada</country></aff></contrib-group><author-notes><corresp id="an0001"><label>*</label>Correspondence to: Thomas M Durcan; Email: <email xlink:href="thomas.durcan@mcgill.ca">thomas.durcan@mcgill.ca</email></corresp><fn><p>Punctum to: Durcan, TM, Tang, MY, Dashti, EA, Aguileta, MA, Gros, P, Shaler, TA and Fon, EA (2014) USP8 Regulates Mitophagy by Removing K6-linked Ubiquitin Conjugates from Parkin. The EMBO Journal; 33(21): 2473-91.</p></fn></author-notes><pub-date pub-type="epub"><day>20</day><month>2</month><year>2015</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2015</year></pub-date><volume>11</volume><issue>2</issue><fpage seq="22">428</fpage><lpage>429</lpage><history><date date-type="received"><day>3</day><month>12</month><year>2014</year></date><date date-type="rev-recd"><day>8</day><month>12</month><year>2014</year></date><date date-type="accepted"><day>9</day><month>12</month><year>2014</year></date></history><permissions><copyright-statement>© 2015 Taylor & Francis Group, LLC</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Taylor & Francis Group, LLC</copyright-holder></permissions><self-uri content-type="pdf" xlink:href="kaup-11-02-1009794.pdf"></self-uri><abstract><p>The Parkinson disease (PD)-associated E3-ubiquitin (Ub) ligase PARK2/parkin plays a central role in many stress response pathways, and in particular, in mitochondrial quality control. Within this pathway, PARK2 activation is accompanied by a robust increase in its autoubiquitination, followed by clearance of the damaged mitochondria by selective autophagy (mitophagy). Yet, little is known about how this auto-ubiquitination is regulated during mitophagy. In our study, we demonstrate that PARK2 forms predominantly K6-linked Ub conjugates on itself. Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway. When USP8 is silenced, a persistence of K6-linked Ub conjugates on PARK2 delays both its translocation to damaged mitochondria and successful completion of mitophagy. Taken together, these findings implicate a novel role for K6-linked Ub conjugates and USP8-mediated deubiquitination in the regulation of PARK2 in mitochondrial quality control.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords</title><kwd>deubiquitination</kwd><kwd>K6 Ub-linkages</kwd><kwd>mitophagy</kwd><kwd>PARK2/Parkin</kwd><kwd>USP8</kwd></kwd-group><counts><fig-count count="1"></fig-count><table-count count="0"></table-count><ref-count count="0"></ref-count><page-count count="2"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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