线粒体
骨骼肌
新陈代谢
细胞生物学
动作(物理)
生物
化学
生物化学
解剖
物理
量子力学
作者
Zhenqi Zhou,Alice Ma,Timothy M. Moore,Dane M. Wolf,Nicole L. Yang,Peter Tran,Mayuko Segawa,Alexander R. Strumwasser,Wei Ren,Kai Fu,Jonathan Wanagat,Alexander M. van der Bliek,Rachelle H. Crosbie‐Watson,Marc Liesa,Linsey Stiles,Rebeca Acín‐Pérez,Sushil K. Mahata,Orian S. Shirihai,Mark O. Goodarzi,Michal K. Handzlik,Christian M. Metallo,David W. Walker,Andrea L. Hevener
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-04-05
卷期号:10 (14)
标识
DOI:10.1126/sciadv.adl0389
摘要
The dynamin-related guanosine triphosphatase, Drp1 (encoded by Dnm1l ), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with DNM1L is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice. Reduced fatty acid oxidation and impaired insulin action along with increased muscle succinate was observed in Drp1-KD muscle. Muscle Drp1-KD reduced complex II assembly and activity as a consequence of diminished mitochondrial translocation of succinate dehydrogenase assembly factor 2 (Sdhaf2). Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. Drp1 is critical in maintaining mitochondrial complex II assembly, lipid oxidation, and insulin sensitivity, suggesting a mechanistic link between mitochondrial morphology and skeletal muscle metabolism, which is clinically relevant in combatting metabolic-related diseases.
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