Role of glucose metabolism and ATP in maintaining PINK1 levels during Parkin-mediated mitochondrial damage responses.

ABSTRACT: Mutations in several genes, including PINK1 and Parkin, are known to cause autosomal recessive cases of Parkinson disease in humans. These genes operate in the same pathway and play a crucial role in mitochondrial dynamics and maintenance. PINK1 is required to recruit Parkin to mitochondria and initiate mitophagy upon mitochondrial depolarization. In this study, we show that PINK1-dependent Parkin mitochondrial recruitment in response to global mitochondrial damage by carbonyl cyanide m-chlorophenylhydrazine (CCCP) requires active glucose metabolism. Parkin accumulation on mitochondria and subsequent Parkin-dependent mitophagy is abrogated in glucose-free medium or in the presence of 2-deoxy-D-glucose upon CCCP treatment. The defects in Parkin recruitment correlate with intracellular ATP l

SUBMITTER: Lee S 

PROVIDER: S-EPMC4294517 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature