Effect of a new monocarboxylic acid antibiotic, A204, on the monovalent cation permeability of rat liver mitochondria

Abstract

A newly isolated polyether monocarboxylic acid antibiotic, A204, is reported here to affect the translocation of monovalent cations across mitochondrial membrane. At 1 μM, A204 caused a complete inhibition of glutamate oxidation in valinomycin or monazomycin-treated rat liver mitochondria in a K + medium. The antibiotic has the following ion specificity: K + = Rb +>Na + = Cs +>Li +. Pyridine nucleotides in intact mitochondria became oxidized upon addition of A204; however, A204 did not affect respiration supported by succinate oxidation. It also causes the leakage of K +, transient release of H +, and decrease of mitochondrial volume. The monovalent cation-dependent hydrolysis of ATP in valinomycin- or monazomycin-treated mitochondria was first activated and then inhibited at concentrations of A204 above 2 μM. The inhibitory effect of A204 on adenosine triphosphatase (ATPase) is also ion dependent, but it is equally supported by Na +, K + and Rb +. We can therefore classify A204 as a new ionophore with properties shared by its predecessors, monensin, nigericin and dianemycin, which induce ion permeability in biological membranes.