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Mitochondrial fission governed by Drp1 regulates exogenous fatty acid usage and storage
bioRxiv - Cell Biology Pub Date : 2020-10-22 , DOI: 10.1101/2020.10.17.343616
Jae Eun Song , Tiago C. Alves , Bernardo Stutz , Matija Sestan-Pesa , Nicole Kilian , Sabrina Diano , Richard G. Kibbey , Tamas L. Horvath

The bioenergetic function of mitochondrial fission is associated with uncoupled respiration or elimination of damaged mitochondria to maintain a healthy mitochondrial population. In the presence of a high abundance of exogenous fatty acids, cells can either store fatty acids in lipid droplets or oxidize them in mitochondria. Even though carnitine palmitoyltransferase-1 (CPT1) controls the respiratory capacity of mitochondria in fatty acid oxidation, we observed that it did not dictate the balance of storage and usage of lipids in HeLa cells. On the other hand, inhibition of mitochondrial fission by silencing dynamic-related protein 1 (DRP1) resulted in an increase in fatty acid content of lipid droplets and a decrease in fatty acid oxidation. Mitochondrial fission was not only reflective of the amount of exogenous fatty acid being processed by mitochondria, but also found to be actively involved 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.

中文翻译:

由Drp1控制的线粒体裂变调节外源脂肪酸的使用和储存

线粒体裂变的生物能功能与不相关的呼吸作用或消除受损的线粒体有关,以维持健康的线粒体种群。在存在大量外源脂肪酸的情况下,细胞可以将脂肪酸存储在脂质小滴中或将其氧化在线粒体中。即使肉碱棕榈酰转移酶-1(CPT1)控制了线粒体在脂肪酸氧化中的呼吸能力,但我们观察到它并不决定HeLa细胞中脂质的储存和使用之间的平衡。另一方面,通过使动态相关蛋白1(DRP1)沉默来抑制线粒体裂变,导致脂质滴的脂肪酸含量增加,而脂肪酸氧化减少。线粒体裂变不仅反映了线粒体加工的外源脂肪酸的量,而且还积极参与了线粒体和脂滴之间脂肪酸的分布。我们的数据揭示了线粒体裂变的新功能,可以在使用和存储之间平衡外源脂肪酸,为线粒体动力学控制细胞内燃料利用和分配发挥作用。
更新日期:2020-10-27
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