Heterogeneity of monoamine oxidase activities in synaptic and non-synaptic mitochondria derived from three brain regions: some functional implications.

The heterogeneity of monoamine oxidase (MAO; EC 1.4.3.4) activities was studied in two fractions of synaptic mitochondria (SM & SM2) and one fraction of non-synaptic ("free") mitochondria (M) isolated from three rat brain regions (cerebral cortex, striatum, and pons & medulla) by the Lai and Clark (1979, 1989) method in order to elucidate the heterogeneity of MAO at the subcellular and brain regional levels. The activities toward serotonin (MAO-A), benzylamine (MAO-B), and dopamine (MAO-DA) in SM2 from all three regions were different from the corresponding values in SM. In addition, the various MAO activities in SM and SM2 showed heterogeneous distribution with respect to the three brain regions investigated. Both the distribution of MAO-A and MAO-B in non-synaptic mitochondria (M) did not show marked regional differences although MAO-DA in M varied depending on the region. These results clearly demonstrate that the distribution of MAO activities toward different substrates is heterogeneous both at the subcellular and the brain regional levels. The MAO-A:MAO-B ratios in the various mitochondrial fractions also showed trends that are consistent with this hypothesis. Furthermore, in fraction SM of synaptic mitochondria, this ratio was consistently higher than values in the other two mitochondrial fractions (SM2 & M) irrespective of the region from which they were isolated. In view of the functional importance of MAO in the regulation and compartmentation of amine metabolism, the heterogeneity of MAO at subcellular and regional levels may assume pathophysiological importance in neurological diseases (e.g., Parkinsonism) with which altered amine metabolism is associated.