Mitochondrial prohibitins (PHB) are highly evolutionarily 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. SGK-1 belongs to the AGC kinase family and is the sole C. elegans homologue of the mammalian Serum- and Glucocorticoid-inducible Kinase. SGK-1 regulates aging and mitochondrial homeostasis as part of TORC2 downstream of RICT-1. Intriguingly, TORC2 mutants induce the mitochondrial unfolded protein response (UPRmt), while reducing the strong UPRmt elicited by PHB depletion. Here we show that
sgk-1 mutants have increased mitochondrial size, mitochondrial interconnectivity, respiration rate and ROS production. Remarkably, all these features are suppressed by PHB depletion. A transcription factor RNAi screen identified lipid and sterol homeostasis as UPRmt modulators in
sgk-1 mutants. Further, we show that
sgk-1 mutants have impaired lipogenesis and lipoprotein/yolk formation, plausibly due to alterations in membrane lipid and sterol homeostasis. Surprisingly, both defects are suppressed by PHB depletion. Lifespan analysis shows the requirement of the sterol binding protein SRBP1/SBP-1 for the extended lifespan of
sgk-1 mutants and the further increase conferred by PHB depletion. Additionally, we show that while autophagy is similarly induced in
sgk-1 mutants, PHB-depleted and
sgk-1;PHB-depleted animals, lysosomal function is particularly enhanced in
sgk-1;PHB-depleted worms. Interestingly, autophagy and the UPRmt are dispensable for the lifespan of
sgk-1 mutants and PHB-depleted animals. However, the enhanced longevity caused by PHB depletion in
sgk-1 mutants requires both, the UPRmt and autophagy, but not mitophagy. We hypothesize that UPRmt induction upon PHB depletion extends lifespan of
sgk-1 mutants through autophagy and probably modulation of lipid metabolism.