Metabolic control analysis and mitochondrial function in the nerve terminal

Abstract

Reduced activities of the mitochondrial electron transport chain complexes have been implicated in the pathogenesis of numerous neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Metabolic control analysis (MCA) was used to investigate the spread of control among the respiratory chain components, complex I, complex II/III and complex IV over oxygen consumption in in situ mitochondria in rat brain synaptosomes. The results provide information on the control possessed by the complexes and the level by which the complexes can be inhibited before deleterious effect are imposed on mitochondrial function. The results show that complex I possessed the highest level of control of the complexes examined, over synaptosomal oxygen consumption. Complex I had the highest flux control coefficient and lowest inhibition threshold of the complexes examined. The complex I threshold was determined to be - 10%, which would imply that the 30 - 40% decrease in complex I activity reported in PD could be inducing detrimental effects on mitochondrial function.