Accumulation of calcium and phosphate stimulated by carboxylic antibiotics into mitochondria

Carboxylic ionophores such as nigericin, dianemycin, the monensins and compounds Lilly A 217 or X-537 A, stimulate an electron-transport dependent accumulation of Ca 2+ and phosphate into mitochondria. Ion accumulation is stimulated under conditions of limited Ca 2+ 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 Ca 2+ 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 Ca 2+ and phosphate on β-hydroxybutyrate oxidation, into tightly coupled state 3 to 4 transitions. Evidence suggests that electrophoretic Ca 2+ transport occurs in parallel with proton or K + carriers. The anion movements associated to Ca 2+ uptake are most probably driven by the existent ΔpH across the mitochondrial membrane.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44799/1/10863_2005_Article_BF01516075.pd