Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis

Enkler, Ludovic and Szentgyörgyi, Viktoria and Pennauer, Mirjam and Prescianotto-Baschong, Cristina and Riezman, Isabelle and Wiesyk, Aneta and Avraham, Reut Ester and Spiess, Martin and Zalckvar, Einat and Kucharczyk, Roza and Riezman, Howard and Spang, Anne. (2023) Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis. Nature Cell Biology , 25 (8). pp. 1157-1172.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spang)
UniBasel Contributors:Spang, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Oct 2023 03:10
Deposited On:14 Aug 2023 10:11

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