Using a linear model of oxidative phosphorylation (Samartsev V.N., Kozhina O.V., Polishchuk L.S. H Biophysics. 2005. V. 50. No 4. P. 660-667), functional activity of liver mitochondria was studied and the effects of inhibition of electron transport in respiratory chain by malonate and of activation of passive proton leak by 2,4-dinitrophenol (DNP) were assessed. It is shown that, in addition to the accepted indicators of the mitochondrial functional activity, such parameters its the state of oxidation subsystem (V-OX), activity of phosphorilation subsystem (V-P), and activity of passive proton leak (V-L) can be used. These parameters are independent of each other and describe electron transport in respiratory chain, ATP synthesis, and passive proton leak, respectively. The model was further applied to estimate a functional state of rat liver mitochondria following a per os administration of a toxic mixture containing yttrium oxide, barium nitrate and copper hydrooxicarbonate (toxic stress). It is shown that within 3 hours after the toxic mixture application (20 or 100 mg/kg of body mass), an increase of respiration rate in state 4 occurred. No changes in state 3 were recorded, either during succinate oxidation or during pyruvate and malate oxidation. A decrease of P/O ratio indicating the uncoupling of oxidative phosphorilation, and the reduction of the ATP synthesis rate were observed only during pyruvate and malate oxidation. The changes of respiration and P/O ratio changes could be described by the model assuming that toxic stress induced a passive proton leak without influence on the ATP synthesis (increase in VI., no change in V-P, and increase in V-OX during succinate oxidation only). The P/O ratio (lid not decrease during succinate oxidation because of the increase of the electron transport rate in the respiratory chain. 7 days after the administration of the toxic mixture at a dose of 20 mg/kg all the parameters returned to a normal level. The observed change in the functional state of the mitochochondria induced by toxic stress may be an early nonspecific reaction of the general adaptive syndrome.
