PT  - JOURNAL ARTICLE
AU  - Matoba, Satoaki
AU  - Kang, Ju-Gyeong
AU  - Patino, Willmar D.
AU  - Wragg, Andrew
AU  - Boehm, Manfred
AU  - Gavrilova, Oksana
AU  - Hurley, Paula J.
AU  - Bunz, Fred
AU  - Hwang, Paul M.
TI  - p53 Regulates Mitochondrial Respiration
AID  - 10.1126/science.1126863
DP  - 2006 Jun 16
TA  - Science
PG  - 1650--1653
VI  - 312
IP  - 5780
4099  - http://science.sciencemag.org/content/312/5780/1650.short
4100  - http://science.sciencemag.org/content/312/5780/1650.full
SO  - Science2006 Jun 16; 312
AB  - 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.