PPTC7 limits mitophagy through proximal and dynamic interactions with BNIP3 and NIX.

ABSTRACT: PPTC7 is a mitochondrial-localized PP2C phosphatase that maintains mitochondrial protein content and metabolic homeostasis. We previously demonstrated that knockout of Pptc7 elevates mitophagy in a BNIP3- and NIX-dependent manner, but the mechanisms by which PPTC7 influences receptor-mediated mitophagy remain ill-defined. Here, we demonstrate that loss of PPTC7 upregulates BNIP3 and NIX post-transcriptionally and independent of HIF-1α stabilization. On a molecular level, loss of PPTC7 prolongs the half-life of BNIP3 and NIX while blunting their accumulation in response to proteasomal inhibition, suggesting that PPTC7 promotes the ubiquitin-mediated turnover of BNIP3 and NIX. Consistently, overexpression of PPTC7 limits the accumulation of BNIP3 and NIX protein levels in respo

SUBMITTER: Wei L 

PROVIDER: S-EPMC10849627 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature