| Popis: |
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) mutantssgk-1andrict-1. Here, we show thatsgk-1mutants have impaired mitochondrial homeostasis, lipogenesis, yolk formation and autophagy flux due to alterations in membrane lipid and sterol homeostasis. Remarkably, all these features are suppressed by PHB depletion. Lifespan analysis shows that autophagy and the mitochondrial unfolded protein response (UPRmt), but not mitophagy, are required for the enhanced longevity caused by PHB depletion insgk-1mutants. We hypothesize that UPRmtinduction upon PHB depletion extends lifespan ofsgk-1mutants through autophagy. Our results strongly suggest that PHB depletion suppresses the autophagy defects ofsgk-1mutants by altering membrane lipid composition at ER-mitochondria contact sites, where TORC2 localizes. |
