Ion Transport by Heart Mitochondria: VII. ACTIVATION OF THE ENERGY-LINKED ACCUMULATION OF Mg++ BY Zn++ AND OTHER CATIONS

Abstract

Abstract The effect of a number of heavy metal ions on the energy-linked accumulation of Mg++ by isolated heart mitochondria has been studied with the use of ascorbate and tetramethylphenylenediamine as the energy source. With this substrate Mg++ uptake is activated strongly by Zn++ and Cd++, and to a lesser degree by Cu++, Hg++, and Ag+. In contrast to this activation of Mg++ accumulation, these reagents depress oxidative phosphorylation and the energy-linked accumulation of Ca++. The cation-dependent increase in Mg++ accumulation requires phosphate or arsenate and is inhibited by inhibitors of respiration and uncouplers of phosphorylation. It is strongly inhibited by adenosine diphosphate and by sulfhydryl group reagents, but is insensitive to oligomycin. It is also depressed by Na+ and K+. The increased ion uptake in the presence of Zn++ is accompanied by increased respiration. This observation is consistent with a greater demand for free energy to support the increased ion accumulation. Zn++ has little effect on the loss of accumulated ions to the suspending medium, and appears to act by stimulating the rate of uptake of Mg++. A large portion of the available Zn++ is taken up by the mitochondria in a reaction which does not require the expenditure of free energy. Mitochondria which are tightly coupled accumulate Mg++ rather slowly compared to preparations which show poorer respiratory control. Mg++ accumulation in tightly coupled mitochondria is activated to a greater degree by Zn++ and Cd++ than is the corresponding reaction in more loosely coupled preparations. It is suggested that specific membrane lesions which favor the energy-linked uptake of Mg++ can be induced by the addition of Zn++ or Cd++, and perhaps by other procedures. The relationship of the Zn++-dependent uptake of Mg++ to other induced ion transport systems of the mitochondrion is discussed.