RT Journal Article
T1 Prohibitin depletion extends lifespan of a TORC2/SGK-1 mutant through autophagy and the mitochondrial UPR
A1 Pérez-Jiménez, Mercedes M.
A1 de la Cruz Ruiz, Patricia
A1 Hernando Rodriguez, Blanca
A1 Rodríguez Palero, María Jesús
A1 Martínez-Bueno, Manuel D.
A1 Pla, Antoni
A1 Gatsi, Roxani
A1 Artal-Sanz, Marta
K1 Autophagy
K1 Lipogenesis
K1 Mitochondria
K1 Prohibitin
K1 SGK-1
K1 UPRmt
AB Mitochondrial prohibitins (PHB) are highly conserved proteins with a peculiar effecton lifespan. While PHB depletion shortens lifespan of wild-type animals, it enhanceslongevity of a plethora of metabolically compromised mutants, including target ofrapamycin complex 2 (TORC2) mutants sgk-1 and rict-1. Here, we show that sgk-1mutants have impaired mitochondrial homeostasis, lipogenesis and yolk formation,plausibly due to alterations in membrane lipid and sterol homeostasis. Remarkably, allthese features are suppressed by PHB depletion. Our analysis shows the requirementof SRBP1/SBP-1 for the lifespan extension of sgk-1 mutants and the further extensionconferred by PHB depletion. Moreover, although the mitochondrial unfolded proteinresponse (UPR mt ) and autophagy are induced in sgk-1 mutants and upon PHB deple-tion, they are dispensable for lifespan. However, the enhanced longevity caused byPHB depletion in sgk-1 mutants requires both, the UPR mt and autophagy, but not mi-tophagy. We hypothesize that UPR mt induction upon PHB depletion extends lifespanof sgk-1 mutants through autophagy and probably modulation of lipid metabolism.
PB Aging Cell. Wiley-Blackwell
YR 2021
FD 2021-05-03
LK https://hdl.handle.net/10433/26309
UL https://hdl.handle.net/10433/26309
LA en
NO Aging Cell. 2021;20:e13359.
NO Universidad Pablo de Olavide. Departamento de Biología Molecular e Ingeniería Bioquímica
DS RIO
RD May 9, 2026