Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control.

ABSTRACT: The deglycase and chaperone protein DJ-1 is pivotal for cellular oxidative stress responses and mitochondrial quality control. Mutations in PARK7, encoding DJ-1, are associated with early-onset familial Parkinson's disease and lead to pathological oxidative stress and/or disrupted protein degradation by the proteasome. The aim of this study was to gain insights into the pathogenic mechanisms of selected DJ-1 missense mutations, by characterizing protein-protein interactions, core parameters of mitochondrial function, quality control regulation via autophagy, and cellular death following dopamine accumulation. We report that the DJ-1^M26I mutant influences DJ-1 interactions with SUMO-1, in turn enhancing removal of mitochondria and conferring increased cellular susceptibili

SUBMITTER: Strobbe D 

PROVIDER: S-EPMC5862874 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature