Molecular chaperone-mediated rescue of mitophagy by a Parkin RING1 domain mutant.

ABSTRACT: Mitochondrial dysfunction is characteristic of many neurodegenerative diseases. The Parkinson's disease-associated ubiquitin-protein ligase, Parkin, is important in the elimination of damaged mitochondria by autophagy (mitophagy) in a multistep process. Here, we show that a Parkin RING domain mutant (C289G) fails to redistribute to damaged mitochondria and cannot induce mitophagy after treatment with the mitochondrial uncoupler carbonyl cyanide m-methylhydrazone, because of protein misfolding and aggregation. Parkin(C289G) aggregation and inclusion formation were suppressed by the neuronal DnaJ/Hsp40 chaperone HSJ1a(DNAJB2a). Importantly, HSJ1a and DNAJB6 also restored mitophagy by promoting the relocation of Parkin(C289G) and the autophagy marker LC3 to depolarized mitochondria. The rescu

SUBMITTER: Rose JM 

PROVIDER: S-EPMC3000674 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature