The interaction of zinc pyrithione with mitochondria from rat liver and a study of the mechanism of inhibition of ATP synthesis

The interactions of zinc pyrithione (ZnPT) with rat liver mitochondria were investigated. Since most of the organometals, principally the triorganotin compounds, induce the inhibition of ATP synthesis in rat liver mitochondria, the efficiency of the ATP synthesis was measured in the presence of ZnPT. The results indicate that ZnPT inhibits ATP synthesis. In order to individuate the molecular mechanism responsible for a failure in ATP synthesis, all of the steps involved in ATP synthesis or in its inhibition were investigated separately, i.e. the respiratory chain, the uncoupling effect, the ATPase and the opening of a permeability pore. All of the steps are inhibited by ZnPT, but the crucial one, the one responsible for the inhibition of ATP synthesis, seems to be the opening of a small-size cyclosporine-sensitive pore. The results are different from those obtained using other organometallic compounds, but are similar to those obtained when using methylmercury and Zn2+, both of which also induce the opening of a cyclosporine-sensitive pore. However, although Hg2+ and Zn2+ would seem to induce the opening of large-size pores, in the case of ZnPT the pores involved are of a small size. This action mechanism seems to exclude the possibility that ZnPT is a deliverer of Zn2+. Copyright (C) 2003 John Wiley Sons, Ltd.