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The mitochondrial prohibitin complex, a context-dependent modulator of longevity, has broad effects in the C. elegans metabolome, suggesting a remodelling of the mitochondrial respiratory chain

AuthorsBastos Lourenço, Artur; Burgess, Karl; Artal-Sanz, Marta
Issue Date2017
CitationVI Spanish Worm Meeting (2017)
AbstractThe mitochondrial prohibitin (PHB) complex, composed of two proteins, PHB-1 and PHB-2, is a context-dependent modulator of longevity. Specifically, PHB deficiency shortens the lifespan of otherwise wild type worms, while it dramatically extends lifespan under compromised metabolic conditions, as is the case of insulin-receptor daf-2(e1370) mutants. This extremely intriguing phenotype has been linked to alterations in mitochondrial function and in fat metabolism. However, the true function of the PHB complex remains elusive. To understand the impact that PHB depletion has on aging, we undertook mass spectrometry-based metabolomics and lipidomics approaches. These top-down approaches raised different working hypothesis that we are currently exploring. PHB depletion has a major effect on the metabolome, being the effect much more pronounced in wild type than in daf-2 mutant worms. In particularly, it highlighted that PHB depletion in either wild type or daf-2 mutant animal’s has a differential effect in triglycerides composition, in parallel with a diffferential effect on riboflavin, and nicotinate and nicotinamide metabolism. This led us to hypothesize that PHB has a direct or indirect effect on the mitochondrial respiratory chain (MRC), resulting in differential energy energy effciency. Preliminary results by blue-native gel analysis of enriched mitochondrial fractions indicate that PHB has a differential effect on the mitochondrial respiratory chain of wild type and daf-2 mutant animals. Consistently, oxygen consumption rate measurements using a Seahorse XFp Analyzer points to a differential effect of PHB depletion in the different genetic backgrounds during aging. These new findings will be discussed in the scope of the opposing longevity phenotype caused by PHB depletion.
DescriptionResumen del póster presentado al VI Spanish Worm Meeting, celebrado en Valencia del 9 al 10 de marzo de 2017.
Appears in Collections:(CABD) Comunicaciones congresos
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