Mathematical model of regulation of oxidative phosphorylation in intact mitochondria.

1. A mathematical model of the regulation of mitochondrial ATP synthesis by the extramitochondrial ATP/ADP ratio is presented taking into account the transport processes of phosphate and of adenine nucleotides by their specific translocators. 2. In agreement with known experimental data the model describes the control of respiration by the extramitochondrial ATP/ADP ratio as well as the distribution of adenine nucleotides and of inorganic phosphate between the extramitochondrial and the intramitochondrial compartment. 3. In the extramitochondrial compartment the phosphorylation potential is predicted by the model to be higher than in the matrix space. 4. Despite the differences in the phosphorylation potentials no particular translocation energy is necessary. This has been achieved by postulating a charge compensation between the movement of adenine nucleotides and the uptake of phosphate during ATP synthesis. 5. The proton stoichiometry of the proton pump must be higher than stated by the chemiosmotic coupling hypothesis in its present form, otherwise sufficient results could not be obtained. 6. With increasing activities of non-phosphorylating energy requiring side reactions (as uncoupling) at first the difference of the respiration rates between the phosphorylating and the non-phosphorylating state disappears, at higher activities the ADP phosphorylation stops, but the membrane potential collapses at very high activities only.