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dc.contributor.authorNarendra, Derek P.
dc.contributor.authorJin, Seok Min
dc.contributor.authorTanaka, Atsushi
dc.contributor.authorSuen, Der-Fen
dc.contributor.authorGautier, Clement A.
dc.contributor.authorShen, Jie
dc.contributor.authorCookson, Mark R.
dc.contributor.authorYoule, Richard J.
dc.date.accessioned2012-02-25T01:48:24Z
dc.date.issued2010
dc.identifier.citationNarendra, Derek P., Seok Min Jin, Atsushi Tanaka, Der-Fen Suen, Clement A. Gautier, Jie Shen, Mark R. Cookson, and Richard J. Youle. 2010. PINK1 Is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biology 8(1): e1000298.en_US
dc.identifier.issn1544-9173en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8255738
dc.description.abstractLoss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pbio.1000298en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811155/pdf/en_US
dash.licenseLAA
dc.titlePINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkinen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Biologyen_US
dash.depositing.authorGautier, Clement A.
dc.date.available2012-02-25T01:48:24Z
dash.affiliation.otherHMS^Neurology-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Neurology-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pbio.1000298*
dash.contributor.affiliatedTanaka, Atsushi
dash.contributor.affiliatedGautier, Clement A.
dash.contributor.affiliatedShen, Jie


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