On the nature of electron and energy transport in mitochondria II. Multiple activation of mitochondrial respiration

Abstract

1. Combinations of uncoupling agents with various electron transfer inhibitors suggest that State 4 is only an endogenously inhibited State 3. 2. Combinations of two uncouplers provide a tool for detecting differences in their behavior. It is concluded that dicoumarol may act only on phosphorylation Sites 2 and 3, and dinitrophenol and dibromophenol on all three of them. 3. Experiments with combinations of: (1) uncoupler plus ADP, (2) uncoupler plus substrate, and (3) substrate plus ADP, suggest a strong competition between substrate, uncoupler and ADP for a common receptor system. 4. It is concluded that at least two hypotheses can explain the results. Hypothesis 1, taking into account the mechanisms of oxidative phosphorylation suggested by Chance 2 and Slater 3, places the point of interaction of substrate, uncoupler and ADP at the junction between electron and energy transfer chains, and Hypothesis 2, based on the observations of Van Dam and co-workers 15–17 and the suggestions of Van Dam and Slater 20, places it in the active-transport mechanism of the membrane itself.