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线粒体脂肪酸合成协调哺乳动物线粒体中的氧化代谢。

Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria.

机构信息

Department of Biochemistry, Salt Lake City, United States.

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, United States.

出版信息

Elife. 2020 Aug 17;9:e58041. doi: 10.7554/eLife.58041.

DOI:10.7554/eLife.58041
PMID:32804083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7470841/
Abstract

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 mutant mouse skeletal myoblast cell lines 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.

摘要

细胞中存在两种脂肪酸合成系统，一种位于细胞质中（由脂肪酸合酶 FASN 催化），另一种位于线粒体中（mtFAS）。与 FASN 不同，mtFAS 的特征研究较少，特别是在高等真核生物中，其主要产物、代谢作用和细胞功能基本未知。在这里，我们发现功能减弱的 mtFAS 突变体小鼠成肌细胞系显示出电子传递链 (ETC) 复合物的严重缺失，并表现出代偿性代谢活性，包括还原羧化作用。这种对 ETC 复合物的影响似乎与蛋白 lipoylation 无关，lipoylation 是 mtFAS 的最佳特征功能，因为缺乏 lipoylation 的突变体具有完整的 ETC。最后，mtFAS 损伤会阻止体外成肌细胞的分化。总之，这些数据表明哺乳动物的 ETC 活性受到 mtFAS 功能的深刻调控，从而将合成脂肪酸的合成与碳燃料的氧化联系起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/150c2450e22c/elife-58041-resp-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/f6b33fab381c/elife-58041-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/7e61cb935b49/elife-58041-fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/fd143f6d282c/elife-58041-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/be275c7300bd/elife-58041-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/6d710f63ff95/elife-58041-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/fc887541c673/elife-58041-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/61bc482b6896/elife-58041-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/76e547d398bf/elife-58041-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/cf5f85a36413/elife-58041-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/150c2450e22c/elife-58041-resp-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/f6b33fab381c/elife-58041-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/57b9a19559ff/elife-58041-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/034167552e86/elife-58041-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/5a0bdfc35838/elife-58041-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/7e61cb935b49/elife-58041-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/4354068c9751/elife-58041-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/fd143f6d282c/elife-58041-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/be275c7300bd/elife-58041-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/6d710f63ff95/elife-58041-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/fc887541c673/elife-58041-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/61bc482b6896/elife-58041-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/76e547d398bf/elife-58041-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/cf5f85a36413/elife-58041-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54a/7470841/150c2450e22c/elife-58041-resp-fig2.jpg

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