Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death

The mechanisms beyond the Warburg effect in proliferative mammalian cells, as well as for the similar Crabtree effect in the yeast Saccharomyces cerevisiae, are still a matter of debate: why do cells shift from the energy-efficient respiration to the energy-inefficient fermentation at high sugar concentration? This review reports on the strong similarities of these phenomena in both cell types, discusses the current ideas, and provides a novel interpretation of their common functional mechanism in a dynamic perspective. This is achieved by analyzing another phenomenon, the sugar-induced-cell-death (SICD) occurring in yeast at high sugar concentration, to highlight the link between ATP depletion and cell death. The integration between SICD and the dynamic functioning of the glycolytic process, suggests a fitness advantage of the Crabtree/Warburg effect in the long term, which consists in the maintenance of the cell energetic homeostasis, therefore strategic for cell survival.