Calcium transport by rat brain mitochondria and oxidation of 2-oxoglutarate

Contrary to previous reports brain mitochondria have a substantial capacity for net Ca²⁺ uptake (approx. 1.2 μeq. Ca²⁺ per mg protein) providing succinate is the oxidizable substrate. ATP stimulates calcium uptake (to 1.8 μeq. per mg protein), but is not required. The accumulation of Ca²⁺ with NAD-linked substrates is, however, significantly less. With 2-oxoglutarate, very limited Ca²⁺ uptake occurs before respiration is inhibited. At low concentrations (10 μM), Ca²⁺ stimulates the 2-oxoglutarate dehydrogenase activity of detergent solubilized mitochondria. Millimolar [Ca²⁺] is required for inhibition. Therefore, Ca²⁺ inhibition of 2-oxoglutarate oxidation can explain the low maximum uptake with this substrate, but probably not by directly effecting the dehydrogenase. Hence, the oxidation of 2-oxoglutarate can be either enhanced or suppressed depending upon the net Ca²⁺ accumulated by brain mitochondria.