{"doi":"10.1016/j.isci.2020.101015","title":"MCL-1 Inhibition by Selective BH3 Mimetics Disrupts Mitochondrial Dynamics Causing Loss of Viability and Functionality of Human Cardiomyocytes","abstract":"MCL-1 is a well-characterized inhibitor of cell death that has also been shown to be a regulator of mitochondrial dynamics in human pluripotent stem cells. We used cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) to uncover whether MCL-1 is crucial for cardiac function and survival. Inhibition of MCL-1 by BH3 mimetics resulted in the disruption of mitochondrial morphology and dynamics as well as disorganization of the actin cytoskeleton. Interfering with MCL-1 function affects the homeostatic proximity of DRP-1 and MCL-1 at the outer mitochondrial membrane, resulting in decreased functionality of hiPSC-CMs. Cardiomyocytes display abnormal cardiac performance even after caspase inhibition, supporting a nonapoptotic activity of MCL-1 in hiPSC-CMs. BH3 mimetics targeting MCL-1 are promising anti-tumor therapeutics. Progression toward using BCL-2 family inhibitors, especially targeting MCL-1, depends on understanding its canonical function not only in preventing apoptosis but also in the maintenance of mitochondrial dynamics and function.","journal":"iScience","year":2020,"id":55650,"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":91,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":288310,"name":"Nilay Taneja","orcid":"0000-0002-9046-0953","position":1,"is_corresponding":false},{"id":288311,"name":"Abigail C. Neininger","orcid":"0000-0001-5104-4407","position":2,"is_corresponding":false},{"id":288312,"name":"Lili Wang","orcid":"0000-0003-4276-3930","position":3,"is_corresponding":false},{"id":288313,"name":"Gabriella L. Robertson","orcid":"0000-0002-8729-8334","position":4,"is_corresponding":false},{"id":290242,"name":"Stellan Riffle","orcid":null,"position":5,"is_corresponding":false},{"id":288314,"name":"Linzheng Shi","orcid":"0000-0002-2571-2798","position":6,"is_corresponding":false},{"id":236808,"name":"Björn C. Knollmann","orcid":"0000-0003-4956-9735","position":7,"is_corresponding":false},{"id":288315,"name":"Dylan T. Burnette","orcid":"0000-0002-2571-7038","position":8,"is_corresponding":false},{"id":288316,"name":"Vivian Gama","orcid":"0000-0002-1201-1394","position":9,"is_corresponding":false},{"id":288309,"name":"Megan L. Rasmussen","orcid":"0000-0002-8056-6092","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T21:05:29.672878Z","pmid":"32283523","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":[]}