Action of potassium atractylate on oxidative phosphorylation in mitochondria and in submitochondrial particles

Abstract

1. 1. Atractylate inhibits the ATP-P 1 exchange and the 2,4-dinitrophenol-stimulated ATPase activity. It does not act on the ADP-ATP exchange nor on the adenylate kinase activity. 2. 2. In intact mitochondria, atractylate inhibits to the same extent the ATP-P 1 exchange, the β-hydroxybutyrate oxidation and the coupled phosphorylation. 3. 3. In digitonin fragments, the ATP-P 1 exchange is strikingly inhibited by a amounts of atractylate which do not affect the rate of β-hydroxybutyrate oxidation and do not uncouple oxidative phosphorylation. 4. 4. ATP synthesis coupled to oxidation of β-hydroxybutyrate or of succinate by hypotonically pretreated mitochondria is much less inihibited by atractylate than the ATP-P 1 exchange. In contrast, the phosphorylation linked to the oxidation of reduced cytochrome c by oxygen remains as much inhibited by atractylate as the ATP-P 1 exchange. 5. 5. Inhibitory effects of atractylate and of reduction of the respiratory chain on the 2,4-dinitrophenol-stimulated ATPase and on the ATP-P 1 exchange are additive in the case of digitonin fragments. 6. 6. Inhibition of the ATP-P 1 exchange by atractylate is maximal when the concentration of inorganic phosphate is high. 7. 7. Atractylate does not prevent the mitochondrial swelling initiated by inorganic phosphate or by hypotonic conditions. Inorganic phosphate potentiates the inhibitory effect of atractylate on the ATP-induced contraction. 8. 8. The experimental data are discussed with reference to the mechanism of oxidative phosphorylation.