Kravenska I. Permeability transition of mitochondrial inner membrane and its modification by metals cations

The thesis shows, that Са2+, Сd2+ and Zn2+, unlike Pb2+ and Со2+, stimulate the permeability transition of liver mitochondria (MPT). The kinetic analysis of the metal-induced MPT has been performed. This process is mediated by megachannel activation and involves cyclophilin D. Carboxyl groups of the potential-dependent anion channel are involved in the metal-induced MPT. Sulfhydryl groups of the ADP/ATP-antiporter contribute to the Сd2+- and Zn2+-induced MPT. Binding of Са2+ and Zn2+ with cyclophilin D and Сd2+ - with ADP/ATP-antiporter represents key events for the activation of MPT pore. Mitochondrial Na+/Ca2+-exchanger stimulates the metal-induced MPT. In general, it was discovered different mechanisms of the Са2+-, Сd2+- and Zn2+-initiated MPT, swelling of mitochondria and Са2+ release from them under the influence of these cations and also MPT induced by low and high concentrations of Са2+. Obtained differences depend on the ability of metals cations to interact with constituents of MPT pore and on the functional state of other transporting systems of these organelles.