Testosterone enhances mitochondrial complex V function in the substantia nigra of aged male rats.

Deficits in coordinated motor behavior and mitochondrial complex V activity have been observed in aged males. Testosterone supplementation can improve coordinated motor behavior in aged males. We investigated the effects of testosterone supplementation on mitochondrial complex V function in the substantia nigra (a brain region that regulates motor activity) in aged male rats. These rats exhibited diminished ATP levels, attenuated mitochondrial complex V activity, and reduced expression of 3 of the 17 mitochondrial complex V subunits (ATP6, ATP8 and ATP5C1) in the substantia nigra. Testosterone supplementation increased ATP levels, mitochondrial complex V activity, and ATP6, ATP8 and ATP5C1 expression in the substantia nigra of the rats. Conversely, orchiectomy reduced mitochondrial complex V activity, downregulated ATP6 and ATP8 expression, and upregulated ATP5C1, ATP5I and ATP5L expression in the substantia nigra. Testosterone replacement reversed those effects. Thus, testosterone enhanced mitochondrial complex V function in the substantia nigra of aged male rats by upregulating ATP6 and ATP8. As potential testosterone targets, these two subunits may to some degree maintain nigrostriatal dopaminergic function in aged males.