Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.

ABSTRACT: Loss-of-function mutations in the PINK1 and PRKN genes are the most common cause of early-onset Parkinson disease (PD). The encoded enzymatic pair selectively identifies, labels, and targets damaged mitochondria for degradation via the macroautophagy/autophagy-lysosome system (mitophagy). This pathway is cytoprotective and efforts to activate mitophagy are pursued as therapeutic avenues to combat PD and other neurodegenerative disorders. When mitochondria are damaged, the ubiquitin kinase PINK1 accumulates and recruits PRKN from the cytosol to activate the E3 ubiquitin ligase from its auto-inhibited conformation. We have previously designed several mutations that effectively derepress the structure of PRKN and activate its enzymatic functions in vitro. However, it rema

SUBMITTER: Fiesel FC 

PROVIDER: S-EPMC12758189 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature