Protective effect of the plasticizer di(2-ethylhexyl) phthalate against damage of the mitochondrial membrane induced by calcium: possible participation of the adenine nucleotide translocator

Abstract

The effect of di(2-ethylhexyl) phthalate (DEHP) on the response of isolated rat liver mitochondria to Ca 2+ was investigated. DEHP was found to inhibit more than 60% of the auto-accelerating release of respiration induced by 100 μM Ca 2+, being maximally inhibitory at 40 μM. Prior addition of DEHP also partially inhibited Ca 2+-induced swelling of the mitochondrial matrix. However, DEHP did not change the net rate of Ca 2+ uptake measured by the steady-state infusion method. DEHP also reduced the rate of adenine nucleotide exchange across the mitochondrial membrane. Another alkyl phthalate and alkyl citrates had similar effects on Ca 2+-induced membrane damage, but their potencies depended on the lengths of their alkyl chains. These results suggest that the effects of DEHP and other alkyl esters on mitochondrial functions are mainly based on their actions on membrane lipids surrounding adenine nucleotide translocator (AdNT), resulting in alteration of the interaction between these phospholipids and AdNT, and consequent modification of the state of the protein.