Oxidative phosphorylation and mitochondrial physiology: a critical review of chemiosmotic theory, and reinterpretation by the association-induction hypothesis.

Fundamental assumptions of the chemiosmotic hypothesis of Mitchell are examined. Comparison of these assumptions with experimental data accumulated over the past fifty years leads to the conclusion that the hypothesis has not been supported. A review of important findings concerning the physical state of the major intracellular cation potassium shows clearly that this ion does not exist in a free state but is adsorbed on specific anionic sites. These findings refute the membrane-pump theory but added powerful support for the association-induction hypothesis, on the basis of which a new mechanism of oxidative phosphorylation as well as a wide variety of mitochondrial behaviors are proposed and compared with experimental data.