학술논문
Drp1 controls complex II assembly and skeletal muscle metabolism by Sdhaf2 action on mitochondria.
Document Type
Article
Author
Zhenqi Zhou; Ma, Alice; Moore, Timothy M.; Wolf, Dane M.; Yang, Nicole; Tran, Peter; Mayuko Segawa; Strumwasser, Alexander R.; Wenjuan Ren; Kai Fu; Wanagat, Jonathan; van der Bliek, Alexander M.; Crosbie-Watson, Rachelle; Liesa, Marc; Stiles, Linsey; Acin-Perez, Rebecca; Mahata, Sushil; Shirihai, Orian; Goodarzi, Mark O.; Handzlik, Michal
Source
Subject
*MUSCLE metabolism
*SKELETAL muscle
*FATTY acid oxidation
*GUANOSINE triphosphatase
*SUCCINATE dehydrogenase
*INSULIN receptors
*MITOCHONDRIA
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Language
ISSN
2375-2548
Abstract
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. [ABSTRACT FROM AUTHOR]