{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu M"],"funding":["Laboratory for Synthetic Chemistry and Chemical Biology under the Health@InnoHK Program","National Key R&D Program of China","National Key R&D Program of China","MOST | National Natural Science Foundation of China (NSFC)","The strategic priority Research Program of the Chinese academy of sciences","the Fundamental Research Funds for the Central Universities","Center for Advanced Interdisciplinary Science and Biomedicine of IHM of USTC","MOST | National Natural Science Foundation of China"],"pagination":["4923-4949"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12550033"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(20)"],"pubmed_abstract":["While cancer cells overexpress lactate dehydrogenase A (LDHA) to support glycolytic flux and lactate production, the role of LDHB-which preferentially catalyzes lactate oxidation-remains unclear. Here, we demonstrate that LDHB, but not LDHA, is essential for mitotic progression in cancers. During mitosis, CDK1 phosphorylates LDHA at threonine 18, reducing its incorporation into the lactate dehydrogenase (LDH) tetramer. This results in LDHB-enriched tetramers that shift catalytic activity toward lactate oxidation, converting lactate and NAD⁺ into pyruvate and NADH. The generated NADH fuels oxidative phosphorylation and ATP production, thereby sustaining mitosis. Notably, LDHA-T18 phosphorylation occurs exclusively in tumor tissues. Our findings reveal a tumor-specific mechanism in which CDK"],"journal":["EMBO reports"],"pubmed_title":["CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation."],"pmcid":["PMC12550033"],"funding_grant_id":["QYPY20220017","32170736","31970670","2022YFA1303100","YD9100002028","XDB0940101","92357301"],"pubmed_authors":["Wu J","Hou Z","Dai C","Zhang K","Liu M","Cheng A","Du Y","You W","Zhao Y","Ruan K","Yang Z","Gao P","Yang Y","Guo J","Wang T","Zhong F","Shi J","Wu Y"],"additional_accession":[]},"is_claimable":false,"name":"CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation.","description":"While cancer cells overexpress lactate dehydrogenase A (LDHA) to support glycolytic flux and lactate production, the role of LDHB-which preferentially catalyzes lactate oxidation-remains unclear. Here, we demonstrate that LDHB, but not LDHA, is essential for mitotic progression in cancers. During mitosis, CDK1 phosphorylates LDHA at threonine 18, reducing its incorporation into the lactate dehydrogenase (LDH) tetramer. This results in LDHB-enriched tetramers that shift catalytic activity toward lactate oxidation, converting lactate and NAD⁺ into pyruvate and NADH. The generated NADH fuels oxidative phosphorylation and ATP production, thereby sustaining mitosis. Notably, LDHA-T18 phosphorylation occurs exclusively in tumor tissues. Our findings reveal a tumor-specific mechanism in which CDK","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-05T05:49:34.759Z","creation":"2026-06-04T03:06:25.176Z"},"accession":"S-EPMC12550033","cross_references":{"pubmed":["40940446"],"doi":["10.1038/s44319-025-00573-8"]}}