瑞士巴塞尔大学Anne Spang团队发现Arf1协调脂肪酸代谢和线粒体稳态。2023年7月3日出版的《自然—细胞生物学》杂志发表了这项成果。

他们发现在表达小GTPase Arf1的过度活跃突变的细胞中，脂肪酸转运蛋白和参与β-氧化的限速酶的表达减少，导致脂肪酸在脂滴中积累。因此，线粒体分裂，ATP合成减少。脂肪酸的遗传和药理学耗竭使arf1突变体线粒体表型显化。虽然β-氧化发生在哺乳动物的线粒体和过氧化物酶体中，但Arf1在脂肪酸代谢中的作用是保守的。

总之，他们的研究结果表明，Arf1通过调节脂肪酸的储存和利用，以及可能的细胞器接触位点，将代谢整合到能量产生中。

据介绍，在营养短缺期间，脂质动员通过脂肪酸β-氧化是一个必不可少的能量生产过程。在酵母中，这种分解代谢过程始于过氧化物酶体，β-氧化产物从过氧化物酶体进入线粒体并为三羧酸循环提供燃料。人们对这些细胞器之间的物理和代谢合作知之甚少。

附：英文原文

Title: Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis

Author: Enkler, Ludovic, Szentgyrgyi, Viktoria, Pennauer, Mirjam, Prescianotto-Baschong, Cristina, Riezman, Isabelle, Wiesyk, Aneta, Avraham, Reut Ester, Spiess, Martin, Zalckvar, Einat, Kucharczyk, Roza, Riezman, Howard, Spang, Anne

Issue&Volume: 2023-07-03

Abstract: 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.

DOI: 10.1038/s41556-023-01180-2

Source: https://www.nature.com/articles/s41556-023-01180-2