The small GTPase Arf1 regulates ATP synthesis and mitochondria homeostasis by modulating fatty acid metabolism

Enkler, L. and Pennauer, M. and Szentgyörgyi, V. and Prescianotto-Baschong, C. and Riezman, I. and Wiesyk, A. and Kucharczyk, R. and Spiess, M. and Riezman, H. and Spang, A.. (2022) The small GTPase Arf1 regulates ATP synthesis and mitochondria homeostasis by modulating fatty acid metabolism.

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Official URL: https://edoc.unibas.ch/87756/

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Lipid mobilization through fatty acid β-oxidation is a central process essential for energy 36 production during nutrient shortage. In yeast, this catabolic process starts in the peroxisome from where β-oxidation products enter mitochondria and fuel the TCA cycle. Little is known about the physical and metabolic cooperation between these organelles. We found that expression of fatty acid transporters and of the rate-limiting enzyme involved in β-oxidation are decreased in cells expressing a hyperactive mutant of the small GTPase Arf1, leading to an accumulation of fatty acids in lipid droplets. As a consequence, mitochondria became fragmented and ATP synthesis decreased. Genetic and pharmacological depletion of fatty acids phenocopied the arf1 mutant mitochondrial phenotype. Although β-oxidation occurs mainly in mitochondria 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:Preprint
Publisher:Cold Spring Harbor
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
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Last Modified:16 May 2022 14:55
Deposited On:09 Mar 2022 12:03

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