Effect of glucose and deoxyglucose on the redistribution of calcium in Ehrlich ascites tumour and Zajdela hepatoma cells and its consequences for mitochondrial energetics - Further arguments for the role of Ca2+ in the mechanism of the Crabtree effect

The distribution of Ca2+ in intact cells was monitored with fluorescent pro bes: fura-2 for cytosolic [Ca2+] and rhod-2 for mitochondrial [Ca2+]. It wa s found that in neoplastic cells, such as Ehrlich ascites tumour and Zajdel a hepatoma, but not in non-malignant cells, such as fibroblasts, glucose an d deoxyglucose elicited release of Ca2+ from endoplasmic reticulum stores a nd an increase in Ca2+ concentration in the cytosol. parallel to this, a de crease in the rate of Ca2+ extrusion from the cell and an enhanced uptake o f Ca2+ by mitochondria were observed. The increase in mitochondrial [Ca2+] was accompanied by an increase in the mitochondrial membrane potential and the reduction state of nicotinamide nucleotides. F1Fo-ATPase in submitochon drial particles of Zajdela hepatoma was strongly inhibited in the presence of micromolar Ca2+ concentrations, whereas this activity in submitochondria l particles from rat liver appeared to be less sensitive to Ca2+. Indicatio ns of glycosylation of Ehrlich ascites tumour cell proteins were also obtai ned. These data strengthen the proposal [Bogucka, K., Teplova, V.V., Wojtcz ak, L. and Evtodienko, Y. V. (1995) Biochim. Biophys. Acta 1228, 261-266] t hat the Crabtree effect is produced by mobilization of cell calcium, which is subsequently taken up by mitochondria and inhibits F1Fo-ATP synthase.