| First Author | Zhou Z | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 14 | Pages | eadl0389 |
| PubMed ID | 38569044 | Mgi Jnum | J:352334 |
| Mgi Id | MGI:7619442 | Doi | 10.1126/sciadv.adl0389 |
| Citation | Zhou Z, et al. (2024) Drp1 controls complex II assembly and skeletal muscle metabolism by Sdhaf2 action on mitochondria. Sci Adv 10(14):eadl0389 |
| abstractText | 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. |
