Effect of inhibitors and stimulators on isolated liver cell mitochondrial protein synthesis from young and old rats

Mitochondria isolated from the livers of old rats (26-30 months) were found to incorporate 41% less leucine into mitochondrial proteins as compared to those from young rats (2-3 months). The initial rates of incorporation of label were 145 cpm/mg/min for the "old" animals, and 320 cpm/mg/min for the young animal. No difference in either amino acid pool size or leakage of label through the mitochondrial membrane was detected in the two age groups. Young rats were treated in vivo with cycloheximide (10 mg/kg) followed by isolation and incubation of their mitochondria in vitro two hours later. There was a two-fold increase in incorporation of leucine into mitochondrial proteins. In contrast, mitochondria isolated from old rats showed a markedly blunted response to cycloheximide pre-treatment. When mitochondria isolated from young and old rats were exposed to inhibitors of mitochondrial protein synthesis, alpha-alpha-dipyridyl (2 x 10(-4)M) and ethanol (0.15M), the old mitochondria showed greater susceptibility to inhibition. These results suggest that the control of the biosynthesis of mitochondrial proteins is altered in the old animals.