{"doi":"10.1126/sciadv.adl0389","title":"Drp1 controls complex II assembly and skeletal muscle metabolism by Sdhaf2 action on mitochondria","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.","journal":"Science Advances","year":2024,"id":425944,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":871082,"name":"Alice Ma","orcid":"0009-0002-8777-8044","position":1,"is_corresponding":false},{"id":277036,"name":"Timothy M. Moore","orcid":"0000-0003-4250-3370","position":2,"is_corresponding":false},{"id":277039,"name":"Dane M. Wolf","orcid":"0000-0002-0811-1114","position":3,"is_corresponding":false},{"id":1224220,"name":"Nicole L. Yang","orcid":"0000-0002-6684-7939","position":4,"is_corresponding":false},{"id":1224221,"name":"Peter Tran","orcid":"0000-0003-4467-2055","position":5,"is_corresponding":false},{"id":277038,"name":"Mayuko Segawa","orcid":"0000-0002-5680-9576","position":6,"is_corresponding":false},{"id":279698,"name":"Alexander R. Strumwasser","orcid":null,"position":7,"is_corresponding":false},{"id":1224763,"name":"Wenjuan Ren","orcid":null,"position":8,"is_corresponding":false},{"id":1224222,"name":"Kai Fu","orcid":"0000-0002-8107-3556","position":9,"is_corresponding":false},{"id":242288,"name":"Jonathan Wanagat","orcid":"0000-0002-8460-8616","position":10,"is_corresponding":false},{"id":323972,"name":"Alexander M. van der Bliek","orcid":"0000-0002-6211-5765","position":11,"is_corresponding":false},{"id":1224764,"name":"Rachelle H. Crosbie‐Watson","orcid":null,"position":12,"is_corresponding":false},{"id":242292,"name":"Marc Liesa","orcid":"0000-0002-5909-8570","position":13,"is_corresponding":false},{"id":242294,"name":"Linsey Stiles","orcid":"0000-0002-1514-458X","position":14,"is_corresponding":false},{"id":242277,"name":"Rebeca Acín‐Pérez","orcid":"0000-0001-9553-8337","position":15,"is_corresponding":false},{"id":267914,"name":"Sushil K. Mahata","orcid":"0000-0002-9154-0787","position":16,"is_corresponding":false},{"id":242295,"name":"Orian S. Shirihai","orcid":"0000-0001-8466-3431","position":17,"is_corresponding":false},{"id":270034,"name":"Mark O. Goodarzi","orcid":"0000-0001-6364-5103","position":18,"is_corresponding":false},{"id":233745,"name":"Michal K. Handzlik","orcid":"0000-0002-4653-1902","position":19,"is_corresponding":false},{"id":229039,"name":"Christian M. Metallo","orcid":"0000-0003-2404-3040","position":20,"is_corresponding":false},{"id":98564,"name":"David W. Walker","orcid":"0000-0002-9422-2178","position":21,"is_corresponding":false},{"id":277049,"name":"Andrea L. Hevener","orcid":"0000-0003-1508-4377","position":22,"is_corresponding":false},{"id":277035,"name":"Zhenqi Zhou","orcid":"0000-0001-6560-9704","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T01:58:32.160975Z","pmid":"38569044","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}