STUDIES ON THE INHIBITION OF THE MITOCHONDRIAL ATP-ase BY REDUCTION OF THE RESPIRATORY CHAIN

Abstract

The effects of inhibition of the electron transport system on the stimulation of the ATP-ase reaction in liver and rat-heart mitochondria by dinitrophenol were studied. Cyanide at concentrations 10⁻³M and higher effectively reduced the stimulation of ATP-ase by dinitrophenol. A similar but less striking inhibition was observed for rat-heart sarcosomes. This ATP-ase reaction was also inhibited in the presence of 10⁻⁴M cyanide with glutamate, β-hydroxybutyrate, DPNH, and succinate as reductants of the respiratory chain. Anaerobiosis also caused a substantial decrease in the ATP-ase reaction. In all instances, complete inhibition of the ATP-ase reaction could not be achieved when the respiratory chain was reduced. The magnesium-stimulated ATP-ase of rat-heart sarcosomes, of aged mitochondria, and of the Keilin–Hartree heart-muscle preparation was insensitive to reduction of the carriers suggesting that this reaction may constitute only part of the total ATP-ase reaction. The compatability of the various mechanisms of oxidative phosphorylation with these results is discussed.