Fig. 7

Redox control of the cellular energy metabolism. In cancer cells the shift of the metabolism into anaerobic glycolysis is mainly mediated by the PI3K/AKT pathway. AKT activates mTOR, which subsequently activates HIF1α resulting in an induction of GLUT1, enzymes of the glycolysis and the mitochondrial PDK, which inhibits the pyruvate flux into the TCA. The AMPK is able to block this mechanism by inhibition of mTOR to conserve energy. Cancer cells exhibit high ROS (H₂O₂) levels leading to an inhibition of the AMPK and of PTPs, which can inactivate AKT. Even through high H₂O₂ levels DSBs could occur leading to the activation of ATM accompanied with cell cycle arrest. The interaction of ATM and AMPK might enhance the DNA damage response. In addition H₂O₂ might inactivate the PKM2 leading to an altered flux of glucose in the pentose phosphate pathway for the generation of reductions equivalents to detoxify ROS. PDK, pyruvate dehydrogenase kinase; PKM2, pyruvate kinase M2; TCA, tricarboxylic acid.