Prohibitin depletion extends lifespan of a TORC2/SGK-1 mutant through autophagy and the mitochondrial UPR.

ABSTRACT: Mitochondrial prohibitins (PHB) are highly conserved proteins with a peculiar effect on lifespan. While PHB depletion shortens lifespan of wild-type animals, it enhances longevity of a plethora of metabolically compromised mutants, including target of rapamycin complex 2 (TORC2) mutants sgk-1 and rict-1. Here, we show that sgk-1 mutants have impaired mitochondrial homeostasis, lipogenesis and yolk formation, plausibly due to alterations in membrane lipid and sterol homeostasis. Remarkably, all these features are suppressed by PHB depletion. Our analysis shows the requirement of SRBP1/SBP-1 for the lifespan extension of sgk-1 mutants and the further extension conferred by PHB depletion. Moreover, although the mitochondrial unfolded protein response (UPR^mt ) and autophagy are indu

SUBMITTER: de la Cruz-Ruiz P 

PROVIDER: S-EPMC8135086 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature