Induction of Mitochondrial Permeability Transition by the DNA-intercalating Cationic Dye Ethidium Bromide

Abstract

This work shows that the DNA cationic probe, ethidium bromide (EtBr), induces the transition from selective to non-selective mitochondrial permeability. This statement is based on the findings, indicating: (i) EtBr induced the release of accumulated Ca(2+) through a mechanism sensitive to cyclosporin A and octylguanidine; (ii) EtBr induced the release of cytochrome c and (iii) EtBr induced mitochondrial swelling. Interestingly, mersalyl inhibited, in a non-competitive fashion, EtBr uptake, which would indicate that the uptake may be carried out through a protein membrane system. This work also shows that the effect of the dye on permeability transition was stimulated by carboxyatractyloside. Taking into account the facts that EtBr inhibited the ADP exchange reaction and increased the binding of the fluorescent probe eosin-5-maleimide to adenine nucleotide translocase, it is tempting to assume a possible interaction between EtBr and the ADP/ATP carrier.