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Originally published in Science Express on 25 May 2006
Science 16 June 2006:
Vol. 312. no. 5780, pp. 1650 - 1653
DOI: 10.1126/science.1126863
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Reports

p53 Regulates Mitochondrial Respiration

Satoaki Matoba,1 Ju-Gyeong Kang,1 Willmar D. Patino,1 Andrew Wragg,1 Manfred Boehm,1 Oksana Gavrilova,2 Paula J. Hurley,3 Fred Bunz,3 Paul M. Hwang1*

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.

1 Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2 Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
3 Department of Radiation Oncology and Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.

* To whom correspondence should be addressed. E-mail: hwangp{at}mail.nih.gov

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Science. ISSN 0036-8075 (print), 1095-9203 (online)