Regulation of respiration and ATP synthesis in higher organisms: hypothesis.

The present view on the regulation of respiration and ATP synthesis in higher organisms implies only Michaelis-Menten type kinetics and respiratory control as regulatory principles. Recent experimental observations, suggesting further regulatory mechanisms at respiratory chain complexes, are reviewed. A new hypothesis is presented implying regulation of respiration and ATP synthesis in higher organisms mainly via allosteric modification of respiratory chain complexes, in particular of cytochrome c oxidase. The allosteric effectors, e.g., metabolites, cofactors, ions, hormones, and the membrane potential are suggested to change the activity and the coupling degree of cytochrome c oxidase by binding to specific sites at nuclear coded subunits. Recent results on the structure and activity of cytochrome c oxidase, supporting the hypothesis, are reviewed.