Effect of the plasticizer di-(2-ethylhexyl)phthalate on oxidative phosphorylation in rat liver mitochondria: modification of the function of the adenine nucleotide translocator.

The effect of di-(2-ethylhexyl)phthalate (DEHP) on oxidative phosphorylation of isolated rat liver mitochondria was investigated. DEHP at concentrations of 20-1000 microM had no effect on state 4 respiration, but at 40 microM, DEHP decreased the rate of state 3 respiration by about 20%. Although DEHP had no effect on electron transport through the respiratory chain, it decreased the rate of adenosine triphosphate (ATP) synthesis. Its inhibition of ATP synthesis showed a similar concentration dependence to that of state 3 respiration. Furthermore, DEHP at 40 microM inhibited the uptake of [3H]adenosine diphosphate into mitochondria. DEHP also retarded the action of cationic uncoupling agents, which are known to modify the 29000-dalton protein involved in adenine nucleotide exchange. These results suggest that DEHP affects the activity of adenine nucleotide exchange and consequently partially decreases the rate of state 3 respiration. The action of DEHP on the 29000-dalton protein involves a protective effect against mitochondrial damage induced by hydrophobic cations or heavy metal cations.