The effects of the ionophore lysocellin on the movements of Ca²⁺, Mg²⁺ and alkali metal cations and its effect on energy utilization by rat liver mitochondria have been investigated. At a concentration of 0.05 μM, lysocellin induced dissociation of membrane-bound calcium,
and an apparent steady state was established across the inner membrane between energylinked calcium accumulation and the ionophore-induced depletion of calcium. No detectable efflux of intramitochondrial Ca²⁺ and Mg²⁺ was induced by 0.05 μM lysocellin, but the uptake of exogenously added calcium was significantly inhibited. The ionophore augmented Mg²⁺ release from mitochondria induced by Ca²⁺ addition and also caused rapid release of K⁺ from mitochondria preloaded with K⁺ by valinomycin or monazomycin. High levels (0.5-10 μM) of lysocellin caused massive depletion of endogenous Ca²⁺, Mg²⁺ and K⁺ from mitochondria, resulting in disruption of mitochondrial functions including release of state 4 respiration, stimulation of ATPase and inhibition of ADP- or DNP-stimulated respiration. Structureactivity studies with chemically modified compounds of lysocellin indicated the important role of terminal carboxylic acid and C₂₁ hydroxyl function in the activity of the ionophore, and there is a good correlation between the effect of lysocellin on mitochondrial cation movements
and its ability to complex with cations determined in an organic solvent-water two-phase partition system.