Mitochondrial H^+-ATP synthase as a Paralled Condenser

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The head investigator and his coworkers have found many kinds of anisotropic inhibitor of energy transduction (AI) in mitochondria [tetraphenylphosphonium (TPP^+), tetraphenylarsonium, triphenyltetrazolim (TPT^+), and so on] [J.Biol.Chem.255,7631 (1980), Biochim.Biophys.Acta 725,1 (1983)]. Based on these findings, they proposed that positively charged AI (AI^+) inhibits energy transduction by binding to the surface of C-side in redox H^+-pumps and H^+-ATP synthase, in which a negative surface potential is generated in their energized state. Conversely, they considered that negatively charged AI (AI^-) inhibits energy transduction by binding to the surface of M-side in their H^+-pumps, in which a positive surface potential is generated in their energized state. they named it the parallel condenser model of H^+-pumps [in New Functionality Material, Elsevier (1993)].Alternativery, based on the chemiosmotic hypothesis, other workers in this field believe that AI^+ is taken up electrophoret … More ically by mitochondria and then AI^+ inhibits energy transduction of H^+-pumps by acting from their M-side. However, this model cannot explain completely an important phenomenon that the dose-response curve of the energy-dependent binding (or uptake) of AI^+ closely coincides with the dose-response curves for its inhibition of energy transduction in H^+-pumps. The fact indicates that the concentration of AI^+ which causes saturation of the energy-dependent binding of AI^+ to mitochondoria also causes 100% inhibition of the energy transduction in H^+-pumps. If these phenomena occur based on the chemiosmotic model, we would not expect to be able to observe AI^+-induced 100% inhibition of the energy-dependent reactions because complete inhibition of the energy transduction would cause efflux of all the AI^+ taken up in the matrix.We have found in the present project the following findings.1) The surface-potential dependencies of TPP^+-induced H^+-ejection driven by redox H^+-pumps and ATP synthase H^+-pump in mitochondria and of ANS^--binding to submitochondrial particles.2) These is no relationship between the membrane permeability of TPP^+ and TPT^+ in phospholipid bailayr membrane and these AIs^+-induced inhibition of energy transduction in mitochondria. The present findings are in good accord with the parallrl condenser mode of H^+-pumps. Less