Metabolic regulation of Akt: roles reversed

The respiration-deficient, highly glycolytic metabolic phenotype of cancer cells known as the "Warburg effect" has been appreciated for many years. A new study (see Pelicano et al. on p. 913 of this issue) demonstrates that respiration deficiency caused by mitochondrial mutation or hypoxia may directly promote the enormous survival advantage observed in cancer cells by activation of the phosphatidylinositol 3-kinase-Akt survival pathway. We discuss these and other recent findings that show how metabolic changes associated with cancer can play a significant role in tumor biology.