Mechanisms underlying interaction of zinc, lead, and cobalt with nonspecific permeability pores in the mitochondrial membranes

It was demonstrated that Zn 2+, in contrast to Pb 2+ and Co 2+, initiates the development of the nonspecific mitochondrial permeability (NMP) in hepatocytes. Kinetic analysis of this process was performed. It was proved that Zn-induced NMP is mediated by activation of megachannels (mitochondrial permeability transition pores). Sulfo groups of the ADP/ATP antiporter and carboxylic groups of voltage-dependent anionic channels are also involved in the development of Zn 2+-stimulated NMP. Interaction between Zn 2+ and cyclophilin D is the key event in the process of activation of NMP. We found that the Na/Ca exchanger exerts an activating effect on the Zn-induced NMP. In general, swelling of the mitochondria and Ca 2+ release from these organelles under the action of Zn 2+ are based on noticeably dissimilar mechanisms. The observed distinctions depend on the functional state of the mitochondrial transport systems. © 2011 Springer Science+Business Media, Inc.