Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis.

Autor: Enkler L; Biozentrum, University of Basel, Basel, Switzerland., Szentgyörgyi V; Biozentrum, University of Basel, Basel, Switzerland., Pennauer M; Biozentrum, University of Basel, Basel, Switzerland., Prescianotto-Baschong C; Biozentrum, University of Basel, Basel, Switzerland., Riezman I; Department of Biochemistry, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland., Wiesyk A; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland., Avraham RE; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel., Spiess M; Biozentrum, University of Basel, Basel, Switzerland., Zalckvar E; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel., Kucharczyk R; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland., Riezman H; Department of Biochemistry, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland., Spang A; Biozentrum, University of Basel, Basel, Switzerland. anne.spang@unibas.ch.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2023 Aug; Vol. 25 (8), pp. 1157-1172. Date of Electronic Publication: 2023 Jul 03.
DOI: 10.1038/s41556-023-01180-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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