Abstract

Mitochondria oxidize substrates and generate chemical potential in the form of free energy of ATP hydrolysis, which is used to drive various cellular processes. We have developed a computer model of this process (oxidative phosphorylation) consisting of kinetic models of electron transport chain complexes, adenine nucleotide and phosphate transporters, and proton leak. The model was parameterized and validated using dynamic measurements of mitochondrial NADH, reduced cytochrome C, membrane potential and oxygen consumption in rat heart mitochondria. Using our computer model, we report a quantitative description of mitochondrial oxidative phosphorylation when the mitochondria are 1) respiring on endogenous substrates, 2) respiring on added pyruvate and malate at saturating concentrations, and 3) phosphorylating added ADP.

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