[Transamination in the mechanism of protection of mitochondria from Ca2+ overload]

A high sensitivity of the succinate-dependent uptake of Ca2+ by mitochondria to (1) the transamination (TA) substrates glutamate (GLU) and alpha-ketoglutarate (KGL) and (2) the inhibitor of TA aminooxyacetate (AOA) was revealed. The effect of the TA substrates on Ca2+ uptake depends on the ratio (1:10 mM) of their concentrations: 1 mM GLU activates and 10 mM KGL decreases this activation by 35-46%, whereas AOA suppresses the Ca2+ capacity by 60% and the inhibitor of succinate oxidation malonate, by 80-90%. A similarity in the limiting action of KGL and phosphoenolpyruvate (PEP), two sources of oxaloacetate (OAA) and GTP, on Ca2+ capacity was revealed. The differences in the effects of KGL and GLU and the similarity in the effects of KGL and PEP on succinate oxidation are explained by the effect of OAA and GTP on this oxidation. The alternating inflow of OAA in coupled processes of TA, pyruvate cycle, and tricarboxylic acids cycle provides the reciprocal activation and cyclic recurrence of Ca2+ uptake, i. e., protection from the chronic exhausting activation of Ca2+-regulated dehydrogenases, the overload of Ca2+-outgoing channels, and the excessive production of free radicals in mitochondria. The reciprocal regulation of Ca2+ uptake by TA is considered as a mechanism of the maintenance of Ca2+ homeostasis and protection of mitochondria against Ca2+ overload.