In numerous cell types, tumoral cells, proliferating cells, bacteria and yeast, respiration is inhibited when high concentrations of glucose are added to the culture medium. This phenomenon has been named the "Crabtree effect". We used yeast to investigate (i) the short-term event(s) associated to the Crabtree effect and (ii) a putative role of hexoses phosphate in the inhibition of respiration. Indeed yeast divide into 'Crabtree positive' where Crabtree effect occurs and 'Crabtree negative' where it does not. In mitochondria isolated from these two categories of yeast, we found that low, physiological concentrations of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) slightly (20%) stimulated the respiratory flux, and that this effect was strongly antagonized by fructose 1,6-biphosphate (F16bP). On the other hand, F16bP by itself was able to inhibit mitochondrial respiration only in mitochondria isolated from a Crabtree-positive strain. Using permeabilized spheroplasts from Crabtree positive yeast, we have shown that the sole effect observed at physiological concentrations of hexoses phosphate is an inhibition of oxidative phosphorylation by F16bP. This F16bP-mediated inhibition was also observed in isolated rat liver mitochondria, extending this process to mammalian cells. From these results and taking into account that F16bP is able to accumulate in the cell cytoplasm, we propose that F16bP regulates oxidative phosphorylation and thus participates in the establishment of the Crabtree effect.
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|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|