K. Bogucka et al., INHIBITION BY CA2- RELATION TO THE CRABTREE EFFECT( OF THE HYDROLYSISAND THE SYNTHESIS OF ATP IN EHRLICH ASCITES TUMOR MITOCHONDRIA ), Biochimica et biophysica acta. Bioenergetics, 1228(2-3), 1995, pp. 261-266
Phosphorylation of ADP and hydrolysis of ATP by isolated mitochondria
from Ehrlich ascites tumour cells is greatly reduced when the mitochon
dria have been preloaded with Ca2+ (50 nmol/mg protein or more). Trans
location of ADP is diminished in Ca2+-loaded mitochondria. However, AT
Pase in toluene-permeabilized mitochondria and in inside-out submitoch
ondrial particles is also strongly inhibited by micromolar concentrati
ons of Ca2+, indicating that, independently of adenine nucleotide tran
sport, F1F0-ATPase is also affected. ATP hydrolysis by submitochondria
l particles depleted of the inhibitory subunit of F1F0-ATPase (the Pul
lman-Monroy protein inhibitor) is insensitive to Ca2+; however, this s
ensitivity is restored when the particles are supplemented with the in
hibitory subunit isolated from beef heart mitochondria. In view of the
previous observations that glucose elicits in Ehrlich ascites tumour
cells an increase of cytoplasmic free Ca2+ (Teplova, V.V., Bogucka, K.
, Czyz, A., Evtodienko, Yu.V., Duszynski, J. and Wojtczak, L. (1993) B
iochem. Biophys. Res. Commun. 196, 1148-1154) and that this calcium is
then taken up by mitochondria, resulting in a strong inhibition of co
upled respiration (Evtodienko, Yu.V., Teplova, V.V., Duszynski, J., Bo
gucka, K. and Wojtczak, L. (1994) Cell Calcium 15, 439-446), the prese
nt results are discussed in terms of the mechanism of the Crabtree eff
ect in tumour cells.