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Crosstalk between mitochondrial quality control mechanisms and SGK-1 in ageing regulation

AuthorsHernando-Rodríguez, Blanca; Pérez-Jiménez, Mercedes M. ; Pla, Antoni; Rodríguez-Palero, María Jesús ; Artal-Sanz, Marta
Issue Date2017
Citation21st International C. elegans Conference (2017)
AbstractMitochondrial dysfunction triggers the activation of different mitochondrial quality control mechanisms (mtQCM), such as the mitochondrial unfolded protein response (UPRmt), to restore mitochondrial homeostasis, and mitophagy, to degrade damaged mitochondria. Although both mtQCMs have been implicated in the regulation of aging, the underlying molecular mechanisms remains largely elusive. The Serum- and Glucocorticoid-induced Kinase 1 (SGK-1) has been implicated in the regulation of the UPRmt. Long lived sgk-1(ok528) loss of function mutants show a mild induction of the UPRmt. However, under severe mitochondrial stress, like depletion of the mitochondrial prohibitin (PHB) complex that strongly induces the UPRmt, sgk-1(ok538) mutants show reduced UPRmt induction and a further lifespan increase. Remarkably, PHB depletion shortens the lifespan of wild type animals. Given the proposed role of SGK-1 in autophagy inhibition, we set out to investigate the interaction of SGK-1 with mtQCM. In this work, we show that severe mitochondrial stress and mtQCM differentially modulate SGK-1 levels during ageing. While inhibition of either the UPRmt or mitophagy increases SGK-1 protein levels, severe mitochondrial stress reduces SGK-1 levels, triggering autophagy. We further show that under severe mitochondrial stress, only the UPRmt is essential to keep low SGK-1 levels and induce autophagy. Furthermore, both, activation of autophagy and activation of UPRmt are essential for the enhanced longevity of sgk-1(ok538) upon PHB depletion. These data underscores a pivotal role for SGK-1 in the maintenance of mitochondrial homeostasis and underpin the importance of the UPRmt and autophagy for lifespan extension under mitochondrial stress conditions.
DescriptionResumen del trabajo presentado a la 21st International C. elegans Conference of the Genetics Society of America, celebrada en California, Los Angeles (US) del 21 al 25 de junio de 2017.
Appears in Collections:(CABD) Comunicaciones congresos
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