The role of glycolysis-derived hexose phosphates in the induction of the Crabtree effect
Por:
Lemus M.R., Roussarie E., Hammad N., Mougeolle A., Ransac S., Issa R., Mazat J.-P., Uribe-Carvajal S., Rigoulet M., Devin A.
Publicada:
17 ago 2018
Resumen:
Evidence for the Crabtree effect was first reported by H. Crabtree in
1929 and is defined as the glucose-induced decrease of cellular
respiratory flux. This effect was observed in tumor cells and was not
detected in most non-tumor cells. A number of hypotheses on the
mechanism underlying the Crabtree effect have been formulated. However,
to this day, no consensual mechanism for this effect has been described.
In a previous study on isolated mitochondria, we have proposed that
fructose-1,6-bisphosphate (F1,6bP), which inhibits the respiratory
chain, induces the Crabtree effect. Using whole cells from the yeast
Saccharomyces cerevisiae as a model, we show here not only that F1,6bP
plays a key role in the process but that glucose-6-phosphate (G6P), a
hexose that has an effect opposite to that of F1,6bP on the regulation
of the respiratory flux, does as well. Thus, these findings reveal that
the Crabtree effect strongly depends on the ratio between these two
glycolysis-derived hexose phosphates. Last, in silico modeling of the
Crabtree effect illustrated the requirement of an inhibition of the
respiratory flux by a coordinated variation of glucose-6-phosphate and
fructose-1,6-bisphosphate to fit the respiratory rate decrease observed
upon glucose addition to cells. In summary, we conclude that two
glycolysis-derived hexose phosphates, G6P and F1,6bP, play a key role in
the induction of the Crabtree effect.
Filiaciones:
Université Bordeaux, IBGC, UMR 5095, Bordeaux Cedex, France
Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, 1, rue Camille Saint Saëns, Bordeaux Cedex, France
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Université Bordeaux, IBGC, UMR 5095, Bordeaux Cedex, 33077, France
Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, 1, rue Camille Saint Saëns, Bordeaux Cedex, 33077, France
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
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