The effects of oleficin, a polyene antibiotic of the nonmacrolide type, on isolated rat liver mitochondria were studied. Oleficin at a concentration of about 10 nmoles/mg protein increases both the rate of state 4 respiration and the "basal" ATPase activity of mitochondria. In contrast to this it inhibits the rate of both state 3 and uncoupled respiration and the DNP-stimulated ATPase activity. These inhibitions can be prevented by low concentrations (2-5mm) of magnesium ions. Oleficin induces a high amplitude swelling of non-respiring mitochondria in the isoosmotic nitrate and chloride solutions of K
+, Na
+, Tris
+, Tea
+ or Mg
2+. In contrast to that it does not induce swelling of mitochondria treated with ruthenium red in isoosmotic calcium acetate. Indirect evidence suggests that oleficin increases also the proton permeability of the inner membrane. The swelling observed in the isoosmotic solutions of monovalent cations can he prevented by low concentration (2-5mm) of Mg
2+. In the presence of the antibiotic Mg
2+ and Ca
2+ but not K
+ and Na
+, are transferred from an aqueous phase into a butanol-toluene bulk phase. Oleficin depletes Mg
2+ and Ca
2+ from mitochondria in a concentration dependent manner. Complete depletion of Mg
2+ occurs only in the presence of EDTA, while that of Ca
2+ does not need the chelator. It is concluded that the effects of oleficin on mitochondrial functions can be explained on the basis of an increase of the inner membrane permeability as the consequence of the depletion of Mg
2+ from mitochondria caused by the antibiotic.
View full abstract