RT Journal Article
SR Electronic
T1 p53 Regulates Mitochondrial Respiration
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1650
OP 1653
DO 10.1126/science.1126863
VO 312
IS 5780
A1 Matoba, Satoaki
A1 Kang, Ju-Gyeong
A1 Patino, Willmar D.
A1 Wragg, Andrew
A1 Boehm, Manfred
A1 Gavrilova, Oksana
A1 Hurley, Paula J.
A1 Bunz, Fred
A1 Hwang, Paul M.
YR 2006
UL http://science.sciencemag.org/content/312/5780/1650.abstract
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.