In Saccharomyces cerevisiae fructose-1,6-bisphosphate contributes to the Crabtree effect through closure of the mitochondrial unspecific channel

Metabolism of Preimplantation Embryo Development

“…In fact, in some yeasts and some mammalian cells, glucose concentration inversely correlates with OXPHOS activity, a phenomenon known as Crabtree effect (Crabtree, 1929). A number of explanations have been proposed to explain this effect, including competition for ADP and inorganic phosphate (Pi) between glycolysis and OXPHOS, changes in intracellular pH and [Ca 2+ ], and metabolite (such as F1,6BP) suppression of complexes III and IV and/or modulation of mitochondrial unspecific channel (Diaz-Ruiz et al, 2008;Rodriguez-Enriquez, Juarez, RodriguezZavala, & Moreno-Sanchez, 2001; Rosas-Lemus, Uribe-Alvarez, Chiquete-Felix, & Uribe-Carvajal, 2014;Wojtczak, 1996). No matter the specific mechanism, it seems likely that when glucose is abundant, an overflow of EMP pathway by-products likely led to an evolution of a strategy that resulted in maximizing flux through the EMP pathway (via Warburg/ Crabtree effect) in order to increase biomass, and many higher eukaryotes, including humans, utilize a similar strategy (Schuster, Boley, Moller, Stark, & Kaleta, 2015;Vander Heiden et al, 2009).…”

Negative feedback of glycolysis and oxidative phosphorylation: Mechanisms of and reasons for it

“…On the con trary, fructose 1,6 diphosphate addition closes the chan nel and decreases the rate of respiration. It appeared that fructose 1,6 bisphosphate reverses the effect of glucose 6 phosphate, which suggests that fructose 1,6 bisphos phate is the key molecule regulating the activity of ScMUC and the Crabtree effect itself [37].…”

Sensitivity of the Mitochondrial Unspecific Channel ofSaccharomyces cerevisiaeto Butane-1,4-Bisphosphate, a Competitive Inhibitor of Fructose-1,6-Bisphosphate-Aldolase.

“…In isolated mitochondria from S. cerevisiae, glucose‐6‐phosphate stimulates the activity of complex III and partially opens Sc MUC, while F1,6BP inhibits complex III and IV and also closes Sc MUC,i. e. F1,6BP and G6P exhibit opposite effects . The role of F1,6BP in the cell is difficult to evaluate due to its conversion to G6P.…”

“…Hexoses‐phosphate seem to compete at two sites: At high concentration F1,6BP inhibits mitochondrial respiratory complex III and IV, while G6P reverts inhibition. Also, at low concentrationsF1,6BP prevents the mitochondrial permeability transition (PT), which is promoted by G6P …”

“…It has been proposed that MUC is a physiological uncoupling device designed to eliminate cations and decrease production of reactive oxygen species (ROS). The Saccharomyces cerevisiae MUC ( Sc MUC) is closed by, Ca 2+ , Mg 2+ , ADP or F1,6BP, while its opening is mediated by ATP, a decrease in Pi or by high redox pressure …”