Studies on the mechanism of inhibition of the mitochondrial electron transport by antimycin I. Reversal of the inhibition by diethyl ether extraction

Abstract

1. Reversal of antimycin inhibition of succinate oxidation was studied in diethyl ether-extracted heart-muscle preparation and rat-liver mitochondria, respectively. 2. The activity of succinate oxidase in ether-extracted preparations which were not treated with antimycin was completely restored after addition of cytochrome c. Under the same conditions the activity of succinate cytochrome c reductase was increased 2-3-fold. 3. Antimycin-inhibited activity of succinate oxidase and that of succinate cytochrome c reductase was completely restored by extraction of the preparations with diethyl ether providing that soluble cytochrome c was added. 4. Sensitivity of the heart-muscle preparations to antimycin was not affected by extraction with diethyl ether. 5. Antimycin which had been isolated from antimycin-treated preparations was not in any way modified and its capacity to inhibit succinate oxidation was preserved. 6. It was found that a complete reactivation of antimycin-inhibited succinate oxidase could be achieved by ether extraction even when some residual antimycin remained in the preparations. This residual antimycin could be removed by extraction with diethyl ether-ethanol solvent mixture but not by repeated extractions with diethyl ether alone. 7. The results suggest that the reversal of antimycin inhibition by diethyl ether extraction of inhibited preparation was due to the removal of the antibiotic from the site which was responsible for the inhibition of the electron transport chain. However, some bound inhibitor remained at another site which did not directly affect the inhibition.