Abstract

Contrary to previous reports brain mitochondria have a substantial capacity for net Ca 2+ uptake (approx. 1.2 μeq. Ca 2+ 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 Ca 2+ with NAD-linked substrates is, however, significantly less. With 2-oxoglutarate, very limited Ca 2+ uptake occurs before respiration is inhibited. At low concentrations (10 μM), Ca 2+ stimulates the 2-oxoglutarate dehydrogenase activity of detergent solubilized mitochondria. Millimolar [Ca 2+] is required for inhibition. Therefore, Ca 2+ 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 Ca 2+ accumulated by brain mitochondria.

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