Dataset Information

PPTC7 integrates homeostatic and physiological signals to regulate mitophagy and mitochondrial mass

ABSTRACT: Here we report that knockout of PPTC7, a mitochondrial matrix protein, hyperactivates BNIP3/NIX-mediated mitophagy in vitro and in vivo. Biochemically, the PPTC7 precursor is trapped by BNIP3 and NIX to mitochondrial outer-membrane, where PPTC7 scaffolds the assembly of the substrate-PPTC7- SCFFBXL4 holocomplex to degrade BNIP3 and NIX, forming a homeostatic regulatory loop. PPTC7 possesses an unusually weak mitochondrial targeting sequence to facilitate its outer-membrane retention and mitophagy control. Upon starvation, PPTC7 is transcriptionally upregulated in mouse liver to repress mitophagy, which critically maintains hepatic mitochondrial mass, bioenergetics and gluconeogenesis. Collectively, PPTC7 functions as a mitophagy sensor that integrates homeostatic and physiological signals to dynamically control BNIP3 and NIX degradation, thereby maintaining proper mitochondrial mass and cellular homeostasis.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hui Jiang

PROVIDER: PXD042744 | iProX | Mon Jun 05 00:00:00 BST 2023

REPOSITORIES: iProX

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Publications

A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass.

Sun Yuqiu Y Cao Yu Y Wan Huayun H Memetimin Adalet A Cao Yang Y Li Lin L Wu Chongyang C Wang Meng M Chen She S Li Qi Q Ma Yan Y Dong Mengqiu M Jiang Hui H

Molecular cell 20231226 2

Mitophagy mediated by BNIP3 and NIX critically regulates mitochondrial mass. Cellular BNIP3 and NIX levels are tightly controlled by SCF<sup>FBXL4</sup>-mediated ubiquitination to prevent excessive mitochondrial loss and lethal disease. Here, we report that knockout of PPTC7, a mitochondrial matrix protein, hyperactivates BNIP3-/NIX-mediated mitophagy and causes perinatal lethality that is rescued by NIX knockout in mice. Biochemically, the PPTC7 precursor is trapped by BNIP3 and NIX to the mito ...[more]

PMID: 38151018

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Dataset Information

PPTC7 integrates homeostatic and physiological signals to regulate mitophagy and mitochondrial mass

Publications

A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass.

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