title: Analysis of the effect of the mitochondrial prohibitin complex, a context-dependent modulator of longevity, on the C. elegans metabolome.
abstract: The mitochondrial prohibitin complex, composed of two proteins, PHB-1 and PHB-2, is a context-dependent modulator of longevity. Specifically, prohibitin deficiency shortens the lifespan of otherwise wild type worms, while it dramatically extends the lifespan under compromised metabolic conditions. This extremely intriguingly phenotype has been linked to alterations in mitochondrial function and in fat metabolism. However, the true function of the mitochondrial prohibitin complex remains elusive. Here, we used gas chromatography coupled to a flame ionization detector (GC/FID) and ¹H NMR spectroscopy to gain molecular insights into the effect of prohibitin depletion on the Caenorhabditis elegans metabolome. We analysed the effect of prohibitin deficiency in two different developmental stages and under two different conditions, which result in opposing longevity phenotypes, namely wild type worms and daf-2(e1370) insulin signalling deficient mutants. Prohibitin depletion was shown to alter the fatty acid (GC/FID) and ¹H NMR metabolic profiles of wild type animals both at the fourth larval stage of development (L4) and at the young adult (YA) stage, while being more pronounced at the later stage. Furthermore, wild type and the diapause mutant daf-2(e1370), either expressing or not prohibitin, were clearly distinguishable based on their metabolic profiles, revealing changes in fatty acid composition, as well as in carbohydrate and amino acid metabolism. Moreover, the metabolic data indicate that daf-2(e1370) mutants are more robust than the wild type animals to changes induced by prohibitin depletion. The impact of prohibitin depletion on the C. elegans metabolome will be discussed herein in the scope of its effect on longevity. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging. Guest Editor: Aleksandra Trifunovic.
authors.affiliation: Andalusian Centre for Developmental Biology (CABD), CSIC, Universidad Pablo de Olavide-Junta de Andalucía, Carretera de Utrera, km 1, 41013 Sevilla, Spain.
authors.forename: Artur B
authors.initials: AB
authors.lastname: Lourenço
authors.affiliation: Andalusian Centre for Developmental Biology (CABD), CSIC, Universidad Pablo de Olavide-Junta de Andalucía, Carretera de Utrera, km 1, 41013 Sevilla, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Muñoz-Jiménez
authors.affiliation: Department of Biochemistry and Molecular Biology of Plant Products, Instituto de la Grasa (IG-CSIC), Ctra. Utrera Km 1, Campus Universitario Pablo de Olavide, 41013, Sevilla, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Venegas-Calerón
authors.affiliation: Andalusian Centre for Developmental Biology (CABD), CSIC, Universidad Pablo de Olavide-Junta de Andalucía, Carretera de Utrera, km 1, 41013 Sevilla, Spain. Electronic address: martsan@upo.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Artal-Sanz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids / Q000032:analysis; D008136:Longevity; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D008928:Mitochondria / Q000502:physiology*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D000091402:Prohibitins; D012097:Repressor Proteins; C000717335:phb-1 protein, C elegans; C000717338:prohibitin 2, C elegans
keywords: C. elegans; Insulin signalling; Longevity; Metabolomics; Mitochondria; Prohibitin