Mitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism.

TitleMitochondrial quality control mediated by PINK1 and Parkin: links to parkinsonism.
Publication TypeJournal Article
Year of Publication2012
AuthorsNarendra, D, Walker, JE, Youle, R
JournalCold Spring Harb Perspect Biol
Volume4
Issue11
Date Published2012 Nov 01
ISSN1943-0264
KeywordsEnzyme Activation, Mitochondrial Degradation, Mitochondrial Membrane Transport Proteins, Parkinsonian Disorders, Protein Kinases, rho GTP-Binding Proteins, Signal Transduction, Ubiquitin-Protein Ligases, Ubiquitination
Abstract

Mutations in Parkin or PINK1 are the most common cause of recessive familial parkinsonism. Recent studies suggest that PINK1 and Parkin form a mitochondria quality control pathway that identifies dysfunctional mitochondria, isolates them from the mitochondrial network, and promotes their degradation by autophagy. In this pathway the mitochondrial kinase PINK1 senses mitochondrial fidelity and recruits Parkin selectively to mitochondria that lose membrane potential. Parkin, an E3 ligase, subsequently ubiquitinates outer mitochondrial membrane proteins, notably the mitofusins and Miro, and induces autophagic elimination of the impaired organelles. Here we review the recent rapid progress in understanding the molecular mechanisms of PINK1- and Parkin-mediated mitophagy and the identification of Parkin substrates suggesting how mitochondrial fission and trafficking are involved. We also discuss how defects in mitophagy may be linked to Parkinson's disease.

DOI10.1101/cshperspect.a011338
Alternate JournalCold Spring Harb Perspect Biol
Citation Key10.1101/cshperspect.a011338
PubMed ID23125018
PubMed Central IDPMC3536340
Grant ListF30 AG039185 / AG / NIA NIH HHS / United States
MC_U105663148 / / Medical Research Council / United Kingdom
1F30AG039185-01 / AG / NIA NIH HHS / United States
/ / Intramural NIH HHS / United States