Nigericin is a monobasic acid antibiotic originally isolated by Harned et al.1' 2 The antibiotic analyzed for C39H69011 and the molecular weight of the sodium salt was found to be 736. Lardy et al.3 found nigericin and dianemycin to have the unusual property of inhibiting mitochondrial oxidation of glutamate and most other DPN-linked substrates and not inhibiting oxidation or phosphorylation with ,3-hydroxybutyrate or succinate. Nigericin and dianemycin were also observed to inhibit the exchange of P32 between inorganic orthophosphate and ATP. These antibiotics did not uncouple oxidative phosphorylation. 3 In recent studies, nigericin4 and dianemycin were found to inhibit the uptake of K+ induced by monactin or valinomycin in mitochondria. Nigericin and dianemycin cause a rapid loss of alkali metal cations which have accumulated in mitochondria under the influence of a variety of agents. The following is a report of the effect of nigericin on alkali metal cation movements and substrate oxidation in rat liver mitochondria. Experiments with this antibiotic have disclosed an unexpected difference between two groups of substrates with respect to alkali metal cation requirement for oxidation. Experimental Materials and Methods.-Preparation of mitochondria: Mito

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Nigericin, in the concentration range (10(-6) M or higher) at which it uncouples intact mitochondria, was found to increase the conductance of black lipid membranes (BLM) by several orders of magnitude. The dependence of the membrane conductance on pH and K+ concentration suggests a mechanism for the transfer of charge mediated by this ionophore based on a mobile dimer with both nigericin molecules protonated and complexed with one K+. This charged complex accounts for the uncoupling effect observed in intact mitochondria.

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