The effect of aging and acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria

The effect of aging and acute treatment with acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria was studied. The activity of the pyruvate carrier as well as the rates of pyruvate-supported respiration mere both depressed (around 40%) in heart mitochondria from aged rats, the major decrease occurring during the second year of life, Administration of acetyl-L-carnitine to aged rats almost completely restored the rates of these metabolic functions to the level of young control rats, This effect of acetyl-L-carnitine was not due to changes in the content of pyruvate carrier molecules. The heart mitochondrial content of cardiolipin, a key phospholipid necessary for mitochondrial substrate transport, was markedly reduced (approximately 40%) in aged rats. Treatment of aged rats with acetyl-L-carnitine reversed the age-associated decline in cardiolipin content, As the changes in cardiolipin content mere correlated with changes in rates of pyruvate transport and oxidation, it is suggested that acetyl-L-carnitine reverses the age-related decrement in the mitochondrial pyruvate metabolism by restoring the normal cardiolipin content. (C) 1999 Federation of European Biochemical Societies.