Energy sensing and mitochondria: investigating prohibitin genetic interactions

Abstract

Prohibitins are ubiquitous, evolutionarily strongly conserved proteins that localize in mitochondria. Prohibitin depletion shortens life span in wild type worms while, in contrast, in metabolically challenged animals prohibitin depletion promotes life span. We focus on the interactions of prohibitins with the Insulin/IGF-1-like signaling pathway. Mutations in the insulin receptor daf-2 result in strong lifespan extension and probibitin depletion dramatically enhances this phenotype (Artal-Sanz and Tavernarakis, 2009). In order to understand better this opposing effect of prohibitins on lifespan, we looked at genes involved in insulin signalling downstream of daf-2. Interestingly, the only component we identified in the pathway to interact with prohibitins is the sgk-1 gene. Similar to daf-2, depletion of prohibitins in the absence of sgk-1 extends life span. SGK-1 is a serine/threonine protein kinase that is orthologous to the mammalian serumand glucocorticoid-inducible kinases (SGKs) and it acts in parallel to the AKT kinases to mediate DAF-2 signaling for the control of development, stress response, and longevity (Hertweck et al, 2004). Various sources of evidence (Soukas et al, 2009; Jones et al, 2009) have suggested that sgk-1 acts as a receiver of information coming from the Rictor/TORC2 pathway, which is implicated in sensing of the nutrient status of C. elegans, and this information can be further processed to regulate life span. Data on the interaction of prohibitins with SGK-1 in the regulation of lifespan will be discussed.