Accumulation of divalent organic anions by mitochondria

Abstract

Liver mitochondria accumulate and concentrate large quantities of potassium and divalent anions. Potassium is required for organic anion accumulation. Salts of sodium, magnesium or calcium are not accumulated. Both organic (succinate, malate, glutamate) divalent anions, as well as inorganic divalent anions (phosphate, arsenate) are accumulated. Monovalent anions (chloride or fluoride) are not accumulated. All divalent anions tested are competitive inhibitors of each other. Small amounts of uncoupling agents (valinomycin, gramicidin, calcium ions) or diffusible weakly acidic anions, such as acetate or formate, stimulate potassium divalent anion accumulation. Large quantities of the above uncoupling agent block the accumulation process as well as cause the rapid release of accumulated potassium salts from mitochondria. Intramitochondrial accumulation of these alkaline potassium salts results in extramitochondrial acidification. Stoichiometric amounts of acid are produced when the extramitochondrial anion is strongly acidic. Proportionately less extramitochondrial acid is produced when the exterior anion is more weakly acidic. A proposed mechanism for divalent anion accumulation, which is associated with accumulation of potassium, is presented.