{"doi":"10.1101/2025.04.12.648505","title":"The tumour suppressor LACTB remodels mitochondria to promote cytochrome c release and apoptosis","abstract":"Abstract Mitochondria are pivotal regulators of cellular homeostasis, integrating energy metabolism, biosynthesis, and programmed cell death (apoptosis). During apoptosis, mitochondrial outer membrane permeabilization by BAX/BAK pores facilitates release of apoptotic factors, while the role of inner mitochondrial membrane (IMM) remodelling remains less understood. Here, we identify LACTB, a filament-forming serine protease and tumour suppressor, as a regulator of IMM dynamics during apoptosis. LACTB is required for apoptosis-induced IMM remodelling, which in turn causes increased release of cytochrome c and other mitochondrial apoptotic factors. LACTB-induced membrane remodelling is independent of OPA1 processing. Rather, purified LACTB binds and remodels cardiolipin-enriched membrane nanotubes preferentially over planar lipid membranes, suggesting a direct effect in apoptotic membrane remodelling. Intriguingly, LACTB is not required for mitochondrial shape changes induced by mitochondrial depolarization, suggesting that LACTB action is apoptosis-specific. Collectively, our findings establish LACTB as a mediator of apoptosis-induced IMM remodelling, suggesting a mechanism for tumour suppression in cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557545,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"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":514789,"name":"Taewook Kang","orcid":"0000-0002-8704-377X","position":1,"is_corresponding":false},{"id":587904,"name":"Radu V. Stan","orcid":"0000-0003-2969-1725","position":2,"is_corresponding":false},{"id":484496,"name":"Edward J. Usherwood","orcid":"0000-0002-5611-9700","position":3,"is_corresponding":false},{"id":392271,"name":"Henry N. Higgs","orcid":"0000-0002-2917-9644","position":4,"is_corresponding":false},{"id":1366497,"name":"Sukrut C. Kamerkar","orcid":"0000-0003-2848-7132","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:55:17.435961Z","pmid":null,"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":[]}