The Mitochondrial Adenosine Triphosphatase

Abstract

In the previous chapter we saw that the ATPase activity of coupled mitochondria is dramatically stimulated by uncouplers and more generally by conditions that interrupt the flow of energy from the electron transfer chain to the coupling device. These observations have for a long time been interpreted to indicate that the ATPase is involved in the terminal steps of oxidative phosphorylation and that under normal circumstances, i.e., in the coupled state, its primary function is that of an ATP synthetase or kinase. This is supported by the following evidence. 1. There is a good correlation between uncoupling and the appearance of ATPase activity in mitochondria. 2. Isolated components of the ATPase (coupling factors) stimulate oxidative phosphorylation in certain types of submitochondrial particles. 3. Inhibitors of oxidative phosphorylation are also potent inhibitors of the ATPase. 4. Antibodies against the ATPase inhibit oxidative phosphorylation in submitochondrial particles. 5. Purified preparations of the ATPase complex are capable of catalyzing partial reactions of oxidative phosphorylation (e.g., ATP-Pi exchange). 6. Oxidative phosphorylation can be reconstituted in simple systems consisting of a purified respiratory complex and of the ATPase. 7. Membranes that carry out the coupled synthesis of ATP (mitochondria, chloroplasts, bacterial membranes) contain ATPases that are remarkably similar in protein composition and structure.