{"doi":"10.1101/2023.10.02.560316","title":"Selective Mitochondrial Respiratory Complex I Subunit Deficiency Causes Tumor Immunogenicity","abstract":"Abstract Targeting of specific metabolic pathways in tumor cells has the potential to sensitize them to immune-mediated attack. Here we provide evidence for a specific means of mitochondrial respiratory Complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of the CI subunits Ndufs4 and Ndufs6 , but not other subunits, induces an immune-dependent tumor growth attenuation in mouse melanoma models. We show that deletion of Ndufs4 induces expression of the transcription factor Nlrc5 and genes in the MHC class I antigen presentation and processing pathway. This induction of MHC-related genes is driven by an accumulation of pyruvate dehydrogenase-dependent mitochondrial acetyl-CoA downstream of CI subunit deletion. This work provides a novel functional modality by which selective CI inhibition restricts tumor growth, suggesting that specific targeting of Ndufs4 , or related CI subunits, increases T-cell mediated immunity and sensitivity to ICB.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":401015,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":661731,"name":"Tevis Vitale","orcid":"0000-0002-0479-128X","position":1,"is_corresponding":false},{"id":845680,"name":"Xixi Zhang","orcid":"0000-0002-0944-2214","position":2,"is_corresponding":false},{"id":1074651,"name":"Thomas D. Jackson","orcid":"0000-0002-4864-496X","position":3,"is_corresponding":false},{"id":1059434,"name":"Deyang Yu","orcid":"0000-0003-4321-1142","position":4,"is_corresponding":false},{"id":107036,"name":"Mark P. Jedrychowski","orcid":null,"position":5,"is_corresponding":false},{"id":815912,"name":"Steve P. Gygi","orcid":null,"position":6,"is_corresponding":false},{"id":59215,"name":"Hans R. Widlund","orcid":"0000-0002-7506-2447","position":7,"is_corresponding":false},{"id":24148,"name":"Kai W. Wucherpfennig","orcid":"0000-0002-1829-302X","position":8,"is_corresponding":false},{"id":45416,"name":"Pere Puigserver","orcid":"0000-0002-0884-2718","position":9,"is_corresponding":false},{"id":321341,"name":"Jiaxin Liang","orcid":"0000-0003-2129-3626","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37873273","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":[]}