Copper induces permeability transition through its interaction with the adenine nucleotide translocase

In this work we examined the effect of low concentrations of Cu 2+ on the opening of the mitochondrial non‐specific pore. The purpose was addressed to further contribute to the knowledge of the mechanisms that regulate the open/closed cycles of the permeability transition pore. Membrane leakage was established by measuring matrix Ca 2+ efflux and mitochondrial swelling. The experimental results indicate that Cu 2+ at very low concentrations promoted the release of accumulated Ca 2+ , as well as mitochondrial swelling, provided 1,10‐phenanthroline has been added. Carboxyatractyloside and Cu 2+ exhibited additive effects on these parameters. After Cu 2+ titration of membrane thiols, it might be assumed that the blockage of 5.9 nmol of SH/mg protein suffices to open the non‐specific pore. Taking into account the reinforcing effect of carboxyatractyloside, the increasing ADP concentrations, and that N ‐ethylmaleimide inhibited the Cu 2+ ‐induced Ca 2+ efflux, it is proposed that the target site for Cu 2+ is located in the ADP/ATP carrier.