{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mao C"],"funding":["NCI NIH HHS"],"pagination":["1964-1979.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11104512"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["84(10)"],"pubmed_abstract":["The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. F"],"journal":["Molecular cell"],"pubmed_title":["Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers."],"pmcid":["PMC11104512"],"funding_grant_id":["R01 CA269646","P30 CA016672","U54 CA274220","R01 CA247992","R01 CA244144","R01 CA181196"],"pubmed_authors":["Gan B","Kondiparthi L","Lu Z","Lei G","Li Q","Fang B","Yan Y","Olszewski K","Horbath A","Wang M","Liu X","Marszalek JR","Poyurovsky MV","Mao C","Chen X","Zhuang L","Xu Z","Cheng J"],"additional_accession":[]},"is_claimable":false,"name":"Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.","description":"The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. F","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-08T19:53:07.238Z","creation":"2026-04-08T14:31:43.676Z"},"accession":"S-EPMC11104512","cross_references":{"pubmed":["38759628"],"doi":["10.1016/j.molcel.2024.04.009"]}}