The mechanism of mitochondrial swelling: II. Pseudoenergized swelling in the presence of alkali metal salts

Abstract

Alkali metal salts can induce large amplitude swelling of mitochondria in absence of either electron transfer or hydrolysis of ATP. This type of swelling is referred to as pseudoenergized swelling. The requirements for pseudoenergized swelling in salt media have been systematically investigated. The ammonium, sodium, and lithium salts of weakly dissociating acids (e.g., acetate, phosphate, arsenate, phenylacetate) are competent in the induction of rapid swelling when present at 0.15 m concentration whereas the potassium, cesium, and rubidium salts of the same series of acids, at the same concentration, are not competent. The incompetent salts can become competent in presence of one or another reagent of the peptide-antibiotic family (e.g., valinomycin, gramicidin, nigericin). These reagents facilitate selectively the entry of appropriate alkali metal salts into or through the mitochondrial membranes; this facilitation overcomes the distinction between competent and incompetent alkali metal salts. The chlorides of alkali metals as a class are incompetent in inducing pseudoenergized swelling but again the presence of reagents of the peptide-antibiotic family can confer competence. Thus, competence is a function of the rate of penetration of the mitochondrial membranes by the salts in question. Gramicidin shows little or no discrimination with respect to the nature of the alkali metal ion or the nature of the anion in respect to its facilitating action; valinomycin shows some discrimination with respect to the nature of the alkali metal ion; and nigericin is specific for alkali metal salts of weak acids. Cadmium ions at 10 −4 m can duplicate the action of gramicidin in facilitating the induction of pseudoenergized swelling by alkali metal chlorides. This facilitation by cadmium does not extend to the alkali metal acetates. Calcium ions at 10 −4 m also have gramicidin-like action but this action is manifest only after the ions in question have been translocated into the mitochondrion in an energized process. Once inside the mitochondrion, calcium ions have the same capability as does cadmium for potentiating pseudoenergized swelling induced by alkali metal chlorides. Hypotonic swelling is viewed as a special case of pseudoenergized swelling in which the induction is achieved not by exogenous salt but rather by salts contained within the mitochondrion. Three factors play a paramount role in pseudoenergized swelling: (1) the Donnan effect that provides the driving force; (2) the interaction of salt with groups in the membrane that leads to the conformational changes intrinsic to swelling; and (3) the permeability of the membrane that determines which salts are competent in inducing swelling and which are not. Solutes that do not penetrate the mitochondrial membranes can suppress pseudoenergized swelling.