title: Mitochondrial oxidative phosphorylation is regulated by fructose 1,6-bisphosphate. A possible role in Crabtree effect induction?
abstract: 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 with the Crabtree effect and (ii) a putative role of hexose phosphates in the inhibition of respiration. Indeed, yeast divide into "Crabtree-positive," where the 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 and fructose 6-phosphate slightly (20%) stimulated the respiratory flux and that this effect was strongly antagonized by fructose 1,6-bisphosphate (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 hexose phosphates 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.
authors.affiliation: Université Victor Segalen Bordeaux 2, 1 Rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Díaz-Ruiz
authors.forename: Nicole
authors.initials: N
authors.lastname: Avéret
authors.forename: Daniela
authors.initials: D
authors.lastname: Araiza
authors.forename: Benoît
authors.initials: B
authors.lastname: Pinson
authors.forename: Salvador
authors.initials: S
authors.lastname: Uribe-Carvajal
authors.forename: Anne
authors.initials: A
authors.lastname: Devin
authors.forename: Michel
authors.initials: M
authors.lastname: Rigoulet
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013104:Spheroplasts / Q000378:metabolism
chemical_list: D005635:Fructosediphosphates; D019298:Glucose-6-Phosphate; D005947:Glucose; C029063:fructose-1,6-diphosphate