Protein synthesis by hepatic mitochondria isolated from carbon tetrachloride-exposed rats

Abstract

Hepatic mitochondria isolated from rats 40 h after dosage with 1.1 ml/kg CCl 4 are uncoupled and display structural damage. Mitochondrial function returns during hepatic recovery. Because the products of mitochondrial protein synthesis are essential to mitochondrial structure and function, the effects of CCl 4 on the rate of mitochondrial protein synthesis, and on the products, was studied using mitochondria from CCl 4-exposed rats during the early, maximum development and resolution stages of CCl 4-induced mitochondrial damage. Rates of mitochondrial protein synthesis (incorporation of [ 35S]methionine) were elevated 300% over that of mitochondria from non-exposed rats 17 h after exposure; depressed by 50% at 40 h and above control at 113 h. When the radiolabeled products of incorporation were separated and examined by autoradiography, a novel, low-molecular-weight band, of approx. 9700, was apparent 40 h after CCl 4 exposure. A band of similar molecular weight appeared when control mitochondria were incubated without an exogenous supply of ATP. Mitochondria from exposed rats which displayed rates of protein synthesis greater than control consistently had a relative increase in a band that corresponded in size to that of cytochrome oxidase subunit I. It was concluded that the loss of mitochondrial function induced by CCl 4 could not be attributed to inhibition of mitochondrial protein synthesis, and that the mitochondria may not always synthesize protein in constant proportions.