Accumulation of calcium and phosphate stimulated by carboxylic antibiotics into mitochondria

Abstract

Carboxylic ionophores such as nigericin, dianemycin, the monensins and compounds Lilly A 217 or X-537 A, stimulate an electron-transport dependent accumulation of Ca²⁺ and phosphate into mitochondria. Ion accumulation is stimulated under conditions of limited Ca²⁺ loading imposed by phosphate in the presence of β-hydroxybutyrate. Carboxylic ionophores do not affect divalent ion uptake when β-hydroxybutyrate is replaced for by succinate. They block Ca²⁺ and phosphate accumulation when energy is provided from the hydrolysis of ATP, or from the oxidation of glutamate, α-ketoglutarate, pyruvate or glutamate+malate. Nigericin-like antibiotics also transform the indefinite prolongation of state 3 respiration induced by Ca²⁺ and phosphate on β-hydroxybutyrate oxidation, into tightly coupled state 3 to 4 transitions. Evidence suggests that electrophoretic Ca²⁺ transport occurs in parallel with proton or K⁺ carriers. The anion movements associated to Ca²⁺ uptake are most probably driven by the existent ΔpH across the mitochondrial membrane.