Song Jae-Eun, Alves Tiago C, Stutz Bernardo, Šestan-Peša Matija, Kilian Nicole, Jin Sungho, Diano Sabrina, Kibbey Richard G, Horvath Tamas L
Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USA.
Laboratory Medicine, Institute for Clinical Chemistry, Technische Universität Dresden, 01069 Dresden, Germany.
Metabolites. 2021 May 18;11(5):322. doi: 10.3390/metabo11050322.
In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.
在存在大量外源性脂肪酸的情况下，细胞要么将脂肪酸储存在脂滴中，要么在线粒体中氧化它们。在本研究中，我们旨在探索线粒体分裂在HeLa细胞脂质稳态中的一种新的直接作用。我们观察了线粒体形态与响应高外源性脂肪酸时脂滴积累之间的关联。我们通过沉默动力相关蛋白1（DRP1）来抑制线粒体分裂，并观察脂肪酸储存 - 使用平衡的变化。抑制线粒体分裂导致脂滴中脂肪酸含量增加，线粒体脂肪酸氧化减少。接下来，我们过表达肉碱棕榈酰转移酶 - 1（CPT1），这是脂肪酸氧化中的一种关键线粒体蛋白，以进一步研究线粒体脂肪酸利用与线粒体形态之间的关系。线粒体分裂在分配外源性脂肪酸中起作用。CPT1A控制线粒体脂肪酸氧化的呼吸速率，但不会导致脂肪酸在线粒体和脂滴之间的分布发生变化。我们的数据揭示了线粒体分裂在平衡外源性脂肪酸的使用和储存方面的新功能，为线粒体动力学在控制细胞内燃料利用和分配中的作用赋予了新角色。
