{"doi":"10.7554/elife.80919","title":"Differential requirements for mitochondrial electron transport chain components in the adult murine liver","abstract":"Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue-specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD + /NADH ratio, an indicator of cellular redox status. This finding has largely not been tested in vivo. Here, we report that mitochondrial complex I is dispensable for homeostasis of the adult mouse liver; animals with hepatocyte-specific loss of cI function display no overt phenotypes or signs of liver damage, and maintain liver function, redox and oxygen status. Further analysis of cI-deficient livers did not reveal significant proteomic or metabolic changes, indicating little to no compensation is required in the setting of complex I loss. In contrast, complex IV (cIV) dysfunction in adult hepatocytes results in decreased liver function, impaired oxygen handling, steatosis, and liver damage, accompanied by significant metabolomic and proteomic perturbations. Our results support a model whereby complex I loss is tolerated in the mouse liver because hepatocytes use alternative electron donors to fuel the mitochondrial ETC.","journal":"eLife","year":2022,"id":247884,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":272401,"name":"Xun Wang","orcid":"0000-0001-5172-0305","position":1,"is_corresponding":false},{"id":817201,"name":"Zhenkang Chen","orcid":"0000-0002-7919-5546","position":2,"is_corresponding":false},{"id":242253,"name":"Anderson R. Frank","orcid":"0000-0003-2239-9975","position":3,"is_corresponding":false},{"id":817202,"name":"Cameron J. Menezes","orcid":"0000-0001-5759-8099","position":4,"is_corresponding":false},{"id":817607,"name":"Sara House","orcid":null,"position":5,"is_corresponding":false},{"id":817203,"name":"Spencer D. Shelton","orcid":"0000-0003-1236-5317","position":6,"is_corresponding":false},{"id":751447,"name":"Andrew Lemoff","orcid":"0000-0002-4943-0170","position":7,"is_corresponding":false},{"id":251319,"name":"David G. McFadden","orcid":"0000-0001-8466-2199","position":8,"is_corresponding":false},{"id":817204,"name":"Janaka Wansapura","orcid":"0000-0003-0762-2729","position":9,"is_corresponding":false},{"id":262195,"name":"Ralph J. DeBerardinis","orcid":"0000-0002-2705-7432","position":10,"is_corresponding":false},{"id":510119,"name":"Prashant Mishra","orcid":"0000-0003-2223-1742","position":11,"is_corresponding":false},{"id":510117,"name":"Nicholas P. Lesner","orcid":"0000-0001-9734-8828","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T00:23:57.824223Z","pmid":"36154948","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":[]}