Clear Search sequence regions


  • BNIP3 (8)
  • cellular (1)
  • cellular homeostasis (1)
  • gluconeogenesis (1)
  • liver (1)
  • mice (2)
  • PPPTC7 (1)
  • PPTC7 (7)
  • proteolysis (1)
  • regulates (1)
  • repress (1)
  • signals (1)
  • Sizes of these terms reflect their relevance to your search.

    Mitophagy mediated by BNIP3 and NIX critically regulates mitochondrial mass. Cellular BNIP3 and NIX levels are tightly controlled by SCFFBXL4-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 mitochondrial outer membrane, where PPTC7 scaffolds assembly of a 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. Starvation upregulates PPPTC7 expression 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 mitochondrial mass and cellular homeostasis. Copyright © 2023 Elsevier Inc. All rights reserved.

    Citation

    Yuqiu Sun, Yu Cao, Huayun Wan, Adalet Memetimin, Yang Cao, Lin Li, Chongyang Wu, Meng Wang, She Chen, Qi Li, Yan Ma, Mengqiu Dong, Hui Jiang. A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass. Molecular cell. 2024 Jan 18;84(2):327-344.e9

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 38151018

    View Full Text