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A metabolomic perspective of the impact of mitochondrial prohibitin on C. elegans longevity.

AutorLourenço, Artur B.; Muñoz Jiménez, Celia; Cabrerizo Granados, David; Venegas-Calerón, Mónica ; Doherty, Mary; Whitfield, Phillip; Artal-Sanz, Marta
Fecha de publicación24-jun-2015
Citación20th International C. elegans Conference (2015)
ResumenThe mitochondrial prohibitin complex is a context-dependent modulator of longevity. Specifically, prohibitin deficiency shortens the lifespan of otherwise wild type worms, while it dramatically extends lifespan under compromised metabolic conditions, as in the case of the diapause daf-2(e1370) mutant. This extremely intriguingly phenotype has been linked to alterations in mitochondrial function and in fat metabolism. Nevertheless, the true function of the mitochondrial prohibitin complex remains elusive. With the ultimate goal of understanding how mitochondrial prohibitin complex affects longevity, we have employed several metabolomic approaches to characterize the changes elicited upon prohibitin depletion by RNAi on the metabolome of wild type and daf-2 mutant worms.Metabolic analysis by gas chromatography coupled to a flame ionization detector and 1 H-NMR spectroscopy reveals that prohibitin depletion leads to an alteration in the overall fatty acid composition of the worm, as well as in carbohydrate and amino acid metabolism. To enlarge the coverage of the metabolome, we employed a lipidomic mass spectrometry-based approach. We identify that prohibitin has a differential effect in the content of various species of triglycerides and phospholipids in wild type and in daf-2 mutant animals. In particular, we find that prohibitin affects not only the amount but also the composition of fat storage lipids. Overall, prohibitin depletion has a more pronounced effect on the metabolic profiles of wild type worms than of daf-2 mutants indicating that daf-2 mutants are more robust to the changes elicited upon prohibitin depletion. We are currently exploring the relevance of identified metabolites in the context of the effect of prohibitin on the C. elegans longevity.
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