Effect of calcium overload on key dehydrogenases in heart mitochondria

Anotacija

The effect of supra-physiological Ca2+ concentration on the activity of Ca2+- sensitive tricarboxylic cycle dehydrogenases was investigated with the aim to determine if a very fast decrease in mitochondrial NAD(P)H content induced by Ca2+ overload may be caused by changes in activity of these dehydrogenases. We showed that pyruvate and 2-oxoglutarate dehydrogenases in heart mitochondria were stimulated by Ca2+ in the physiological range of concentration but were not affected by Ca2+ overload. In complete contrast, Ca2+ affected isocitrate dehydrogenase (ICDH) only in the supra-physiological range of concentration. The effect of Ca2+ on ICDH depended on isoform and substrate concentration. We showed that in heart mitochondria NADP-ICDH could be from 100 to 350-fold more active than NAD-ICDH. The ratio of their activities decreased with an increase in Ca2+ concentration, because NADP-ICDH was inhibited by Ca2+, while NAD-ICDH was activated. We concluded that among the key mitochondrial dehydrogenases only ICDH isoforms might potentially contribute to Ca2+-overload-induced changes in NAD(P)H concentration. Keywords: heart mitochondria, calcium ions, NAD(P)-dependent dehydrogenases, NAD(P)H