Statistical modelling of mitochondrial power supply

Abstract

By experiment and theory, formulae are derived to calculate the response of mitochondrial power supply, in flux and potential, to an ATP consuming enzyme load, incorporating effects of varying amounts of (i) enzyme, (ii) total circulating adenylate, and (iii) inhibition of the ATP/ADP translocase. The formulae, which apply between about 20% and 80% of maximum respiration, are the same as for the current and voltage of an electrical circuit in which a battery with potential, linear in the logarithm of the total adenylate, charges another battery whose opposing potential is also linear in the same logarithm, through three resistances. These resistances produce loss of potential due to dis-equilibrium of (i) intramitochondrial oxidative phosphorylation, (ii) the ATP/ADP translocase, and (iii) the ATP-consuming enzyme load. The model is represented geometrically by the following configuration: when potential is plotted against flux, the points lie on two pencils of lines each concurrent at zero respiration, the two pencils describing the respective characteristics of the mitochondrion and enzyme. Control coefficients and elasticities are calculated from the formulae.