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© 2010 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Narendra DP, Jin SM, Tanaka A, Suen D-F, Gautier CA, et al. (2010) PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin. PLoS Biol 8(1): e1000298. doi:10.1371/journal.pbio.1000298

Abstract

Loss-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.

Details

Title
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Author
Narendra, Derek P; Jin, Seok Min; Tanaka, Atsushi; Suen, Der-Fen; Gautier, Clement A; Shen, Jie; Cookson, Mark R; Youle, Richard J
Pages
e1000298
Section
Research Article
Publication year
2010
Publication date
Jan 2010
Publisher
Public Library of Science
ISSN
15449173
e-ISSN
15457885
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1294733550
Copyright
© 2010 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Narendra DP, Jin SM, Tanaka A, Suen D-F, Gautier CA, et al. (2010) PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin. PLoS Biol 8(1): e1000298. doi:10.1371/journal.pbio.1000298