Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by fatty acid synthase, FASN) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially in higher eukaryotes, with the major product(s), metabolic roles, and cellular function(s) being essentially unknown. Here we show that hypomorphic mtFAS mutants display a severe loss of electron transport chain (ETC) complexes and exhibit compensatory metabolic activities including reductive carboxylation. This effect on ETC complexes appears to be independent of protein lipoylation, the best characterized function of mtFAS, as mutants lacking lipoylation have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. Together, these data suggest that ETC activity in mammals is profoundly controlled by mtFAS function, thereby connecting anabolic fatty acid synthesis with the oxidation of carbon fuels.

中文翻译：

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线粒体脂肪酸的合成协调线粒体的氧化代谢

细胞具有两种脂肪酸合成系统，一种在细胞质中（由脂肪酸合酶，FASN催化），另一种在线粒体中（mtFAS）。与FASN相比，mtFAS的特性很差，尤其是在高等真核生物中，主要产物，代谢作用和细胞功能基本未知。在这里，我们显示亚型mtFAS突变体显示出严重的电子传输链（ETC）复合物损失，并表现出包括还原性羧化反应在内的代偿性代谢活性。对ETC复合物的这种作用似乎与蛋白质脂酰化作用无关，后者是mtFAS最有特色的功能，因为缺乏脂酰化作用的突变体具有完整的ETC。最后，mtFAS损伤在体外阻断骨骼肌成肌细胞的分化。一起，