Synaptosomal bioenergetics. The role of glycolysis, pyruvate oxidation and responses to hypoglycaemia.

TLDR: It is concluded that synaptosomes are valuable models for studying the control of mitochondrial substrate supply in situ, and pyruvate, but not succinate, is an excellent substrate for intact synaptOSomes.

Abstract: The bioenergetic interaction between glycolysis and oxidative phosphorylation in isolated nerve terminals (synaptosomes) from guinea-pig cerebral cortex is characterized. 1 Essentially all synaptosomes contain functioning mitochondria. 2 There is a tight coupling between glycolytic rate and respiration: uncoupler causes a tenfold increase in glycolysis and a sixfold increase in respiration. 3 Synaptosomes contain little endogenous glycolytic substrate and glycolysis is dependent on external glucose. 4 In glucose-free media, or following addition of iodoacetate, synaptosomes continue to respire and to maintain high ATP/ADP ratios. 5 In contrast to glucose, the endogenous substrate can neither maintain high respiration in the presence of uncoupler nor generate ATP in the presence of cyanide. 6 Pyruvate, but not succinate, is an excellent substrate for intact synaptosomes. 7 The in-situ mitochondrial membrane potential (ΔΨm) is highly dependent upon the availability of glycolytic or exogenous pyruvate; glucose deprivation causes a 20-mV depolarization, while added pyruvate causes a 6-mV hyperpolarization even in the presence of glucose. 8 Inhibition of pyruvate dehydrogenase by arsenite or pyruvate transport by α-cyano-4-hydroxycinnamate has little effect on ATP/ADP ratios; however respiratory capacity is severely restricted. 9 It is concluded that synaptosomes are valuable models for studying the control of mitochondrial substrate supply in situ.