title: RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis.
abstract: Aerobic glycolysis or the Warburg effect contributes to cancer cell proliferation; however, how this glucose metabolism pathway is precisely regulated remains elusive. Here we show that receptor-interacting protein 1 (RIP1), a cell death and survival signaling factor, regulates mitochondrial oxidative phosphorylation and aerobic glycolysis. Loss of RIP1 in lung cancer cells suppressed peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression, impairing mitochondrial oxidative phosphorylation and accelerating glycolysis, resulting in spontaneous DNA damage and p53-mediated cell proliferation inhibition. Thus, although aerobic glycolysis within a certain range favors cancer cell proliferation, excessive glycolysis causes cytostasis. Our data suggest that maintenance of glycolysis by RIP1 is pivotal to cancer cell energy homeostasis and DNA integrity and may be exploited for use in anticancer therapy.
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: 1] Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA [2] Laboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education at Sichuan University, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bai
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: 1] Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA [2] Laboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education at Sichuan University, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Tellez
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: S
authors.initials: S
authors.lastname: Leng
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Padilla
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nyunoya
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Belinsky
authors.affiliation: Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006019:Glycolysis; D006801:Humans; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism*; D009368:Neoplasm Transplantation; D028861:Nuclear Pore Complex Proteins / Q000502:physiology*; D010085:Oxidative Phosphorylation; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000502:physiology*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C119724:AGFG1 protein, human; D028861:Nuclear Pore Complex Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53