PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation
Identifieur interne : 002075 ( Ncbi/Merge ); précédent : 002074; suivant : 002076PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation
Auteurs : Graeme Sargent ; Tim Van Zutphen ; Tatiana Shatseva ; Ling Zhang ; Valeria Di Giovanni ; Robert Bandsma ; Peter Kijun KimSource :
- The Journal of Cell Biology [ 0021-9525 ] ; 2016.
Abstract
Sargent et al. identify the E3 ubiquitin ligase PEX2 as the causative agent of mammalian pexophagy. During amino acid starvation, PEX2 expression increases to ubiquitinate peroxisomal membrane proteins and signal peroxisome degradation by autophagy.
Url:
DOI: 10.1083/jcb.201511034
PubMed: 27597759
PubMed Central: 5021090
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Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation></author><author><name sortKey="Bandsma, Robert" sort="Bandsma, Robert" uniqKey="Bandsma R" first="Robert" last="Bandsma">Robert Bandsma</name><affiliation><nlm:aff id="aff2"><institution>Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><institution>Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, 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sort="Van Zutphen, Tim" uniqKey="Van Zutphen T" first="Tim" last="Van Zutphen">Tim Van Zutphen</name><affiliation><nlm:aff id="aff7"><institution>Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9700 AD Groningen, Netherlands</institution></nlm:aff></affiliation></author><author><name sortKey="Shatseva, Tatiana" sort="Shatseva, Tatiana" uniqKey="Shatseva T" first="Tatiana" last="Shatseva">Tatiana Shatseva</name><affiliation><nlm:aff id="aff6"><institution>Biochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada</institution></nlm:aff></affiliation></author><author><name sortKey="Zhang, Ling" sort="Zhang, Ling" uniqKey="Zhang L" first="Ling" last="Zhang">Ling Zhang</name><affiliation><nlm:aff id="aff3"><institution>Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation></author><author><name sortKey="Di Giovanni, Valeria" sort="Di Giovanni, Valeria" uniqKey="Di Giovanni V" first="Valeria" last="Di Giovanni">Valeria Di Giovanni</name><affiliation><nlm:aff id="aff3"><institution>Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation></author><author><name sortKey="Bandsma, Robert" sort="Bandsma, Robert" uniqKey="Bandsma R" first="Robert" last="Bandsma">Robert Bandsma</name><affiliation><nlm:aff id="aff2"><institution>Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"><institution>Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"><institution>Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation></author><author><name sortKey="Kim, Peter Kijun" sort="Kim, Peter Kijun" uniqKey="Kim P" first="Peter Kijun" last="Kim">Peter Kijun Kim</name><affiliation><nlm:aff id="aff1"><institution>Cell Biology Department, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Biochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada</institution></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Cell Biology</title><idno type="ISSN">0021-9525</idno><idno type="eISSN">1540-8140</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Sargent et al. identify the E3 ubiquitin ligase PEX2 as the causative agent of mammalian pexophagy. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Cell Biol</journal-id><journal-id journal-id-type="iso-abbrev">J. Cell Biol</journal-id><journal-id journal-id-type="publisher-id">jcb</journal-id><journal-id journal-id-type="hwp">jcb</journal-id><journal-title-group><journal-title>The Journal of Cell Biology</journal-title></journal-title-group><issn pub-type="ppub">0021-9525</issn><issn pub-type="epub">1540-8140</issn><publisher><publisher-name>The Rockefeller University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27597759</article-id><article-id pub-id-type="pmc">5021090</article-id><article-id pub-id-type="publisher-id">201511034</article-id><article-id pub-id-type="doi">10.1083/jcb.201511034</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Articles</subject><subj-group><subject>Article</subject></subj-group></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>22</subject><subject>41</subject><subject>35</subject></subj-group></article-categories><title-group><article-title>PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation</article-title><alt-title alt-title-type="short">PEX2 is the E3 ligase for mammalian pexophagy</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sargent</surname><given-names>Graeme</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>van Zutphen</surname><given-names>Tim</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Shatseva</surname><given-names>Tatiana</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Ling</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Di Giovanni</surname><given-names>Valeria</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Bandsma</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-6626-0575</contrib-id><name><surname>Kim</surname><given-names>Peter Kijun</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff6">6</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution>Cell Biology Department, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></aff><aff id="aff2"><label>2</label><institution>Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></aff><aff id="aff3"><label>3</label><institution>Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></aff><aff id="aff4"><label>4</label><institution>Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></aff><aff id="aff5"><label>5</label><institution>Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada</institution></aff><aff id="aff6"><label>6</label><institution>Biochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada</institution></aff><aff id="aff7"><label>7</label><institution>Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9700 AD Groningen, Netherlands</institution></aff><author-notes><corresp id="cor8">Correspondence to Peter K. Kim: <email>pkim@sickkids.ca</email>; or Robert Bandsma: <email>robert.bandsma@sickkids.ca</email></corresp></author-notes><pub-date pub-type="ppub"><day>12</day><month>9</month><year>2016</year></pub-date><volume>214</volume><issue>6</issue><fpage>677</fpage><lpage>690</lpage><history><date date-type="received"><day>09</day><month>11</month><year>2015</year></date><date date-type="accepted"><day>01</day><month>8</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 Sargent et al.</copyright-statement><copyright-year>2016</copyright-year><license license-type="openaccess"><license-p>This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see <ext-link ext-link-type="uri" xlink:href="http://www.rupress.org/terms">http://www.rupress.org/terms</ext-link>). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0/">http://creativecommons.org/licenses/by-nc-sa/3.0/</ext-link>).</license-p></license></permissions><self-uri xlink:role="icon" xlink:href="JCB_201511034_thumb.gif"></self-uri><abstract abstract-type="precis"><p>Sargent et al. identify the E3 ubiquitin ligase PEX2 as the causative agent of mammalian pexophagy. During amino acid starvation, PEX2 expression increases to ubiquitinate peroxisomal membrane proteins and signal peroxisome degradation by autophagy.</p></abstract><abstract><p>Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy. Expression of PEX2 leads to gross ubiquitination of peroxisomes and degradation of peroxisomes in an NBR1-dependent autophagic process. We identify PEX5 and PMP70 as substrates of PEX2 that are ubiquitinated during amino acid starvation. We also find that PEX2 expression is up-regulated during both amino acid starvation and rapamycin treatment, suggesting that the mTORC1 pathway regulates pexophagy by regulating PEX2 expression levels. Finally, we validate our findings in vivo using an animal model.</p></abstract><funding-group><award-group id="sp1"><funding-source>Canadian Institutes of Health Research<named-content content-type="funder-id">http://dx.doi.org/10.13039/501100000024</named-content></funding-source></award-group></funding-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Bandsma, Robert" sort="Bandsma, Robert" uniqKey="Bandsma R" first="Robert" last="Bandsma">Robert Bandsma</name><name sortKey="Di Giovanni, Valeria" sort="Di Giovanni, Valeria" uniqKey="Di Giovanni V" first="Valeria" last="Di Giovanni">Valeria Di Giovanni</name><name sortKey="Kim, Peter Kijun" sort="Kim, Peter Kijun" uniqKey="Kim P" first="Peter Kijun" last="Kim">Peter Kijun Kim</name><name sortKey="Sargent, Graeme" sort="Sargent, Graeme" uniqKey="Sargent G" first="Graeme" last="Sargent">Graeme Sargent</name><name sortKey="Shatseva, Tatiana" sort="Shatseva, Tatiana" uniqKey="Shatseva T" first="Tatiana" last="Shatseva">Tatiana Shatseva</name><name sortKey="Van Zutphen, Tim" sort="Van Zutphen, Tim" uniqKey="Van Zutphen T" first="Tim" last="Van Zutphen">Tim Van Zutphen</name><name sortKey="Zhang, Ling" sort="Zhang, Ling" uniqKey="Zhang L" first="Ling" last="Zhang">Ling Zhang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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