Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia
Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia
Metabolic reprogramming extensively occurs in proliferating cancer cells. This phenomenon occurs highly heterogeneously, but its origin has remained unclear. Here we use a physicochemical concept of free electron potential (FEP) and its equation of state to profile metabolites. We demonstrate that FEP change between substrates and products exactly reflects electrons dissipated in a metabolic transformation. Based on the law of conservation of electron in chemical reactions, a function of FEP change for central metabolism in proliferating cells are further derived, and it can accurately predict metabolic behaviors under hypoxia by maximizing the cellular FEP change to consume electrons. Therefore, enabling electron transfer dictates metabolic reprogramming in hypoxic cells, which underlies the major findings in cancer metabolism and is supported by our experiments. Importantly, our model established on FEP helps to reveal a combination of promising targets to inhibit tumor growth under hypoxia by blocking electron consumption, and could also guide future studies on cancer metabolism under hypoxia.
Ruan Yuxia、Wang Yuanyuan、Cui Yanfen、Li Binghui、Ying Guoguang、Liu Miao、Chen Ceshi、Chu Qiaoyun
Department of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Biochemistry and Molecular Biology, Capital Medical University||Department of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Biochemistry and Molecular Biology, Capital Medical University||Department of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Biochemistry and Molecular Biology, Capital Medical University
肿瘤学生物科学研究方法、生物科学研究技术生物化学
free electron potentialelectron transfermetabolic reprogramminghypoxiamitochondrial dysfunction
Ruan Yuxia,Wang Yuanyuan,Cui Yanfen,Li Binghui,Ying Guoguang,Liu Miao,Chen Ceshi,Chu Qiaoyun.Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/244616.点此复制
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