K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis.

ABSTRACT: Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism, but the underlying biochemical and molecular mechanisms remain elusive. Using a tetracycline inducible model, we show that activation of K-ras(G12V) causes mitochondrial dysfunction, leading to decreased respiration, elevated glycolysis, and increased generation of reactive oxygen species. The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore. Furthermore, pre-induction of K-ras(G12V) expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to

SUBMITTER: Hu Y 

PROVIDER: S-EPMC3257361 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature