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Título: | Metabolomics and aging. The effect of mitochondrial prohibitin complex on the C. elegans metabolome |
Autor: | Lourenço, Artur B.; Muñoz-Jiménez, Celia CSIC; Venegas-Calerón, Mónica CSIC ORCID ; Artal-Sanz, Marta CSIC ORCID | Fecha de publicación: | 2014 | Citación: | XII Symposium on Bioinformatics (2014) | Resumen: | The nematode C. elegans has been extensively used to gain insights in the complex process of aging. Several studies have stressed the existence of a tight link between aging and metabolism. Indeed, marked alterations in the cellular energy metabolism is one universal hallmark of the aging process. Consistently, the biogenesis and function of mitochondria, the energy-generating organelles, is a primary longevity determinant. The mitochondrial prohibitin complex, composed of two proteins, PHB1 and PHB2, which bind to each other to form a heterodimeric bulding block assembled into a ring-like macromolecular structure at the inner mitochondrial membrane, was shown to affect longevity. In particular, while shortening the lifespan of otherwise wild-type animals, prohibitin deficiency increases the lifespan of mutants in insulin signalling pathway (e.g. daf-2(e1370)). Prohibitin deficiency was also shown to affect ATP levels, fat content and mitochondrial proliferation in a genetic-background- and age-specific manner. These findings suggest that prohibitin deficiency may have a broader effect in the metabolome, which might be, at least partially, on the basis of its impact in the aging process. We used gas chromatography coupled to a flame ionization detector (GC-FID) and H-NMR spectroscopy to gain molecular insights on the effect of prohibitin deficiency in the C. elegans metabolome. The free fatty acid (GC-FID) and H-NMR profiles of wild-type (N2) animals at both L4 and young adult (YA) stages revealed a clear distinction between control and phb-1 or phb-2 (RNAi), being this difference more pronounced at YA stage. Furthermore, the GC-FID and H-NMR data clearly distinguished between N2 and daf-2(e1370) mutants, in both control (RNAi) and phb-1 (RNAi), at YA stage. We are currently undertaking mass spectrometry (MS)-based metabolomic approaches aiming to identify the metabolites that change in a prohibitin-dependent manner and/or in a gene tic-background-dependent manner. Our ultimate goal is to pinpoint the metabolic pathways, and more specifically the players, that might be involved in how mitochondrial prohibitin complex affects longevity. | Descripción: | Resumen del trabajo presentado a las XII Jornadas de Bioinformática celebradas en Sevilla (España) del 21 al 24 de septiembre de 2014.-- et al. | URI: | http://hdl.handle.net/10261/130230 |
Aparece en las colecciones: | (CABD) Comunicaciones congresos (IG) Comunicaciones congresos |
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