{"doi":"10.1016/j.celrep.2022.111445","title":"MCL-1 is a master regulator of cancer dependency on fatty acid oxidation","abstract":"MCL-1 is an anti-apoptotic BCL-2 family protein essential for survival of diverse cell types and is a major driver of cancer and chemoresistance. The mechanistic basis for the oncogenic supremacy of MCL-1 among its anti-apoptotic homologs is unclear and implicates physiologic roles of MCL-1 beyond apoptotic suppression. Here we find that MCL-1-dependent hematologic cancer cells specifically rely on fatty acid oxidation (FAO) as a fuel source because of metabolic wiring enforced by MCL-1 itself. We demonstrate that FAO regulation by MCL-1 is independent of its anti-apoptotic activity, based on metabolomic, proteomic, and genomic profiling of MCL-1-dependent leukemia cells lacking an intact apoptotic pathway. Genetic deletion of Mcl-1 results in transcriptional downregulation of FAO pathway proteins such that glucose withdrawal triggers cell death despite apoptotic blockade. Our data reveal that MCL-1 is a master regulator of FAO, rendering MCL-1-driven cancer cells uniquely susceptible to treatment with FAO inhibitors.","journal":"Cell Reports","year":2022,"id":243404,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":454993,"name":"Utsarga Adhikary","orcid":"0000-0002-3122-0837","position":1,"is_corresponding":false},{"id":316423,"name":"Dong Wook Choi","orcid":"0000-0002-5729-2273","position":2,"is_corresponding":false},{"id":309077,"name":"Erika P. Portero","orcid":"0000-0003-4635-515X","position":3,"is_corresponding":false},{"id":136624,"name":"Joao A. Paulo","orcid":"0000-0002-4291-413X","position":4,"is_corresponding":false},{"id":875202,"name":"Pruthvi Gowda","orcid":"0000-0002-3928-2442","position":5,"is_corresponding":false},{"id":256964,"name":"Amit Budhraja","orcid":null,"position":6,"is_corresponding":false},{"id":254774,"name":"Joseph T. Opferman","orcid":"0000-0002-1147-5621","position":7,"is_corresponding":false},{"id":107041,"name":"Steven P. Gygi","orcid":"0000-0001-7626-0034","position":8,"is_corresponding":false},{"id":258928,"name":"Nika N. Danial","orcid":"0000-0003-4842-1827","position":9,"is_corresponding":false},{"id":292188,"name":"Loren D. Walensky","orcid":"0000-0002-0869-2334","position":10,"is_corresponding":false},{"id":454994,"name":"Michelle S. Prew","orcid":"0000-0001-7247-3024","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T00:23:16.032700Z","pmid":"36198266","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":[]}