Fiche publication
Date publication
août 2023
Journal
Nature cell biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ENKLER Ludovic
Tous les auteurs :
Enkler L, Szentgyörgyi V, Pennauer M, Prescianotto-Baschong C, Riezman I, Wiesyk A, Avraham RE, Spiess M, Zalckvar E, Kucharczyk R, Riezman H, Spang A
Lien Pubmed
Résumé
Lipid mobilization through fatty acid β-oxidation is a central process essential for energy production during nutrient shortage. In yeast, this catabolic process starts in the peroxisome from where β-oxidation products enter mitochondria and fuel the tricarboxylic acid cycle. Little is known about the physical and metabolic cooperation between these organelles. Here we found that expression of fatty acid transporters and of the rate-limiting enzyme involved in β-oxidation is decreased in cells expressing a hyperactive mutant of the small GTPase Arf1, leading to an accumulation of fatty acids in lipid droplets. Consequently, mitochondria became fragmented and ATP synthesis decreased. Genetic and pharmacological depletion of fatty acids phenocopied the arf1 mutant mitochondrial phenotype. Although β-oxidation occurs in both mitochondria and peroxisomes in mammals, Arf1's role in fatty acid metabolism is conserved. Together, our results indicate that Arf1 integrates metabolism into energy production by regulating fatty acid storage and utilization, and presumably organelle contact sites.
Mots clés
Animals, Mitochondria, metabolism, Peroxisomes, metabolism, Fatty Acids, metabolism, Oxidation-Reduction, Lipid Metabolism, genetics, Homeostasis, Mammals, metabolism
Référence
Nat Cell Biol. 2023 08;25(8):1157-1172
