{"doi":"10.1126/sciadv.adu4369","title":"Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages","abstract":"Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mitochondria ETC complex III (CIII)-deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow-derived macrophages (BMDMs) isolated from these mitochondria CIII-deficient mice released less IL-10 than controls following TLR3 or TLR4 stimulation. Unexpectedly, restoring mitochondrial respiration without generating superoxide using alternative oxidase (AOX) was not sufficient to reverse LPS-induced endotoxic shock susceptibility or restore IL-10 release. However, activation of protein kinase A (PKA) rescued IL-10 release in mitochondria CIII-deficient BMDMs following LPS stimulation. In addition, mitochondria CIII deficiency did not affect BMDM responses to interleukin-4 (IL-4) stimulation. Thus, our results highlight the essential role of mitochondria CIII-generated superoxide in the release of anti-inflammatory IL-10 in response to TLR stimulation.","journal":"Science Advances","year":2025,"id":509741,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":553688,"name":"Rogan A. Grant","orcid":"0000-0003-0655-0882","position":1,"is_corresponding":false},{"id":841021,"name":"Leah K. Billingham","orcid":null,"position":2,"is_corresponding":false},{"id":618012,"name":"Taylor A. Poor","orcid":"0000-0002-2191-5037","position":3,"is_corresponding":false},{"id":230870,"name":"Samuel E. Weinberg","orcid":"0000-0002-9532-7051","position":4,"is_corresponding":false},{"id":1364798,"name":"Madeline C. Harding","orcid":"0000-0002-2516-8278","position":5,"is_corresponding":false},{"id":468025,"name":"Ziyan Lu","orcid":"0000-0003-2901-3801","position":6,"is_corresponding":false},{"id":294787,"name":"Jason Miska","orcid":"0000-0001-9608-2810","position":7,"is_corresponding":false},{"id":839938,"name":"Marten Szibor","orcid":"0000-0003-4029-160X","position":8,"is_corresponding":false},{"id":230873,"name":"G. R. Scott Budinger","orcid":"0000-0002-3114-5208","position":9,"is_corresponding":false},{"id":104272,"name":"Navdeep S. Chandel","orcid":"0000-0001-7208-3886","position":10,"is_corresponding":false},{"id":634450,"name":"Joshua S. Stoolman","orcid":"0000-0003-3065-9300","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"39841842","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":[]}