[Biological role and mechanisms of realization of the Crabtree effect in rapidly proliferating cells. The role of Ca2+ ions]

Abstract

Characteristic differences in energy supply systems in normal differentiated cells versus rapidly proliferating cells including tumor cells are summarized. Previously suggested mechanisms of the Crabtree effect (inhibition of respiration by glycolysis metabolites) are specifically evaluated. The effect cannot be explained by the competition of glycolysis systems with oxidative phosphorylation for ADP and Pi. A novel mechanism of the Crabtree effect is suggested based on regulatory (inhibitory) effect of Ca2+ as the second messenger on oxidative phosphorylation in tumor cells and other rapidly proliferating cells. The Crabtree effect can be one of the main mechanisms which switch cellular energy metabolism form oxidation to anaerobic glycolysis, the latter being more beneficial for reductive biosynthetic reactions and rapid growth of the cells.