CONTROL OF THE RESPIRATION RATE IN HEART-MITOCHONDRIA - COMPARISON OF THE OXIDATION OF SUCCINATE AND NAD-DEPENDENT SUBSTRATES

The regulation of the respiration of heart mitochondria during the oxidation of FAD- and NAD-dependent substrates (succinate, pyruvate + malate, palmitoylcarnitine) was investigated in the entire range of respiration rates from state 4 to state 3. A creatine kinase ADP-regenerating system was used, permitting stabilization of the concentration of extramitochondrial adenine nucleotides, so that the respiration rate was controlled only by mitochondrial processes. In the entire range of states from state 4 up to 70-80% state 3, respiration was found to be controlled by a DELTA-mu(H)+-consuming system in the oxidation both FAD- and NAD-dependent substrates. The main role in the regulation of respiration close to state 4 is played by proton leakage through the inner mitochondrial membrane, while in the remainder of the indicated range (corresponding to the physiological respiration rates), it is played by the adenine nucleotide translocator (ANT). At the same relative respiration rates, the control coefficient for the ANT proves to be higher, while that for the leakage of protons is lower in the oxidation of NAD-dependent substrates in comparison with succinate. It was established that these differences are due to the fact that the membrane potential is substantially higher at the same relative rate of succinate oxidation than in the case of pyruvate + malate oxidation. The contribution of the DELTA-mu(H)+-consuming system to respiratory control drops sharply, while that of the DELTA-mu(H)+-generating system increases as respiration rates close to the maximum rate in state 3. This phenomenon is more pronounced in the oxidation of a succinate where the control coefficient for ANT drops to zero, while the control coefficient for succinate dehydrogenase increases to 0.7.