Mitochondrial malic enzyme activity is much higher in mitochondria from cortical synaptic terminals compared with mitochondria from primary cultures of cortical neurons or cerebellar granule cells

Most of the malic enzyme activity in the brain is found in the mitochondria . This isozyme may have a key role in the pyruvate recycling pathway which utilizes dicarboxylic acids and substrates such as glutamine to provide pyr uvate to maintain TCA cycle activity when glucose and lactate are low. In t he present study we determined the activity and kinetics of malic enzyme in two subfractions of mitochondria isolated from cortical synaptic terminals , as well as the activity and kinetics in mitochondria isolated from primar y cultures of cortical neurons and cerebellar granule cells. The synaptic m itochondrial fractions had very high mitochondrial melic enzyme (mME) activ ity with a K-m and a V-max of 0.37 mM and 32.6 nmol/min/mg protein and 0.29 mM and 22.4 nmol/min mg protein, for the SM2 and SM1 fractions, respective ly. The K-m and V-max for malic enzyme activity in mitochondria isolated fr om cortical neurons was 0.10 mM and 1.4 nmol/min/mg protein and from cerebe llar granule cells was 0.16 mM and 5.2 nmol/min/mg protein. These data show that mME activity is highly enriched in cortical synaptic mitochondria com pared to mitochondria from cultured cortical neurons. The activity of mME i n cerebellar granule cells is of the same magnitude as astrocyte mitochondr ia. The extremely high activity of mME in synaptic mitochondria is consiste nt with a role for mME in the pyruvate recycling pathway, and a function in maintaining the intramitochondrial reduced glutathione in synaptic termina ls. (C) 2000 Elsevier Science Ltd. All rights reserved.