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 mueq. Ca2+ per mg protein) providing succinate is the oxidizable substrate. ATP stimulates calcium uptake (to 1.8 mueq. 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 microM), 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.