EFFECT OF UNCOUPLING AGENTS AND DETERGENTS ON MOVEMENT OF MONOVALENT CATIONS BETWEEN MITOCHONDRIA AND MEDIUM

The effect of uncouplers of oxidative phosphorylation on the movements of H+ and K+ between isolated rat liver mitochondria and the suspending medium has been studied as a function of initial pH. Such agents induce uptake of H+ at initial pH below 6.5, but as the pH is increased to 7.0 and above, H+ uptake diminishes to zero. At high initial pH, above 8.0, uncoupling agents do not promote loss of H+ from intact mitochondria to the medium. On the other hand, agents known to increase permeability of the mitochondrial membrane, such as the nonionic detergents Lubrol and Triton X-100, induce H+ movements in either direction depending on the initial pH of the extramitochondrial medium. The movements of H+ induced by uncoupling agents are related to (and are controlled by) the opposite translocation of K+ ions. Below pH 7.0, K+ is freely permeable through the membrane, as was shown by direct measurement of K+ loss from mitochondria. Under these conditions H+ can enter in exchange for intramitochondrial K+. At pH above 7.0 K+ cannot go through the membrane, therefore H+ cannot enter. When K+ permeability was increased by addition of valinomycin, then H+ could be ejected from mitochondria in exchange for K+. Uncouplers have also been found to catalyze the exchange of intramitochondrial Ca2+ with extramitochondrial H+, while valinomycin and gramicidin under the same conditions induce the exchange of intramitochondrial Ca2+ with extramitochondrial K+ or Na+, according to their well-known cation specificity. © 1969.