p53 Regulates Mitochondrial Respiration

• Published in: Science (American Association for the Advancement of Science) Vol. 312; no. 5780; pp. 1650 - 1653
• Main Authors: Matoba, Satoaki, Kang, Ju-Gyeong, Patino, Willmar D, Wragg, Andrew, Boehm, Manfred, Gavrilova, Oksana, Hurley, Paula J, Bunz, Fred, Hwang, Paul M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 16.06.2006; The American Association for the Advancement of Science
• Subjects: Adenosine Triphosphate - metabolism; Aging; Animals; Biological and medical sciences; Cancer; Carrier Proteins; Cell Line, Tumor; Cell lines; Cell physiology; Cell Respiration; Cell Survival; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cells; Coefficients; Cytochrome; cytochrome-c oxidase; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Electron Transport Complex IV - physiology; energy; eukaryotic cells; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Gene Expression Regulation, Neoplastic; Genes; Genes, p53; Glycolysis; HCT116 cells; Human genetics; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolism; Mice; Mice, Inbred C57BL; Minerals; mitochondria; Mitochondria - metabolism; Mitochondria, Liver - metabolism; Mitochondrial Proteins; Molecular and cellular biology; Mutation; neoplasm cells; neoplasms; oxygen; Oxygen Consumption; Proteins - genetics; Proteins - physiology; Recombination, Genetic; Respiration; RNA, Small Interfering; Transcription, Genetic; Transcriptional Activation; Tumor Suppressor Protein p53 - physiology; Mitochondria; Regulation(control); TP53 Gene; Respiration; Tumor suppressor gene
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1126863

The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism.