Age-dependent changes in pyruvate uptake by nonsynaptic and synaptic mitochondria from rat brain

Changes in the uptake of pyruvate by nonsynaptic and synaptic mitochondria from brains of young adult and old rats were investigated. An age-dependent decrease in State 3 respiration in the presence of pyruvate plus malate as substrate was observed in cerebral mitochondrial populations but not in liver mitochondria. Addition of exogenous cytochrome c to nonsynaptic and synaptic mitochondria enhanced the rate of State 3 respiration but the age-dependent decrease in State 3 respiration persisted in both types of mitochondria. A decrease in the uptake of pyruvate as measured by the inhibitor-stop and rapid centrifugation techniques was observed in both nonsynaptic and synaptic mitochondria from 24-month-old rats compared to 3-month-old rats. The results suggest that the decrease in the uptake of pyruvate may be one of the factors responsible for the observed reduction in State 3 respiration in the presence of pyruvate plus malate by both nonsynaptic and synaptic mitochondria from brains of senescent rats compared to young adults.