SYNAPTIC AND NON‐SYNAPTIC MITOCHONDRIA FROM RAT BRAIN: ISOLATION AND CHARACTERIZATION

TLDR

Brain mitochondrial heterogeneity and its impact on citric acid cycle compartmentation, including glutamate, aspartate, and 4‑aminobutyrate, are discussed using two proposed metabolic models. The study isolated three mitochondrial populations—two synaptic and one free—characterizing them by enzyme content and substrate oxidation capacity. The isolated populations were heterogeneous in citric acid cycle enzyme activities and substrate utilization, confirming brain mitochondrial diversity and indicating that synaptic mitochondria comprise at least two sub‑populations.

Abstract

Abstract— A method has been developed where by three distinct populations of metabolically active, well coupled and relatively pure mitochondria from rat brain may be prepared. Two mitochondrial populations are derived from synaptozomes and the third consists of ‘free’ (i.e. non‐synaptic) mitochondria. These mitochondrial populations have been characterized with respect to both enzyme content and ability to oxidize substrates. The results indicate that these mitochondrial populations are heterogeneous with respect to maximal activities of certain enzymes concerned with the citric acid cycle and glutamate and 4‐aminobutyrate metabolism as well as their ability to utilize various substrates. The data reported here also confirm that brain mitochondria are very heterogeneous and suggest that synaptic mitochondria may contain at least two sub‐populations. The relations between the heterogeneity of brain mitochondria and the metabolic compartmentation of the citric acid cycle and related metabolites such as glutamate, aspartate and 4‐aminobutyrate are briefly discussed in the light of two proposed models of metabolic compartmentation in the mammalian brain.