{"doi":"10.3389/fphar.2021.712489","title":"Protective Effects of Inhibition of Mitochondrial Fission on Organ Function After Sepsis","abstract":"Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo . Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases.","journal":"Frontiers in Pharmacology","year":2021,"id":168094,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":696661,"name":"Lei Kuang","orcid":"0000-0001-9430-1776","position":1,"is_corresponding":false},{"id":435650,"name":"Yue Wu","orcid":"0009-0005-8031-5292","position":2,"is_corresponding":false},{"id":7292,"name":"Haoyue Deng","orcid":null,"position":3,"is_corresponding":false},{"id":696662,"name":"Han She","orcid":"0000-0001-7497-6995","position":4,"is_corresponding":false},{"id":697348,"name":"Yuanqun Zhou","orcid":null,"position":5,"is_corresponding":false},{"id":426397,"name":"Jie Zhang","orcid":"0000-0002-0466-2955","position":6,"is_corresponding":false},{"id":696663,"name":"Liangming Liu","orcid":"0000-0003-0927-4019","position":7,"is_corresponding":false},{"id":696664,"name":"Tao Li","orcid":"0000-0002-9643-5185","position":8,"is_corresponding":false},{"id":435649,"name":"Yu Zhu","orcid":"0000-0002-0397-8544","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:46:02.603031Z","pmid":"34566637","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":[]}