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

Autor: de la Cruz-Ruiz P; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Hernando-Rodríguez B; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Pérez-Jiménez MM; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Rodríguez-Palero MJ; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Martínez-Bueno MD; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Pla A; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Gatsi R; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain., Artal-Sanz M; Andalusian Centre for Developmental Biology, Consejo Superior de Investigaciones Científicas/Junta de Andalucía/Universidad Pablo de Olavide, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2021 May; Vol. 20 (5), pp. e13359. Date of Electronic Publication: 2021 May 03.
DOI: 10.1111/acel.13359
Abstrakt: 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 induced in sgk-1 mutants and upon PHB depletion, they are dispensable for lifespan. However, the enhanced longevity caused by PHB depletion in sgk-1 mutants requires both, the UPR mt and autophagy, but not mitophagy. We hypothesize that UPR mt induction upon PHB depletion extends lifespan of sgk-1 mutants through autophagy and probably modulation of lipid metabolism.
(© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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