PT  - JOURNAL ARTICLE
AU  - Ludovic Enkler
AU  - Mirjam Pennauer
AU  - Viktoria Szentgyörgyi
AU  - Cristina Prescianotto-Baschong
AU  - Isabelle Riezman
AU  - Aneta Wiesyk
AU  - Roza Kucharczyk
AU  - Martin Spiess
AU  - Howard Riezman
AU  - Anne Spang
TI  - The small GTPase Arf1 regulates ATP synthesis and mitochondria homeostasis by modulating fatty acid metabolism
AID  - 10.1101/2022.01.26.477847
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.26.477847
4099  - http://biorxiv.org/content/early/2022/01/27/2022.01.26.477847.short
4100  - http://biorxiv.org/content/early/2022/01/27/2022.01.26.477847.full
AB  - 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 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.Competing Interest StatementThe authors have declared no competing interest.