CONTROL AND KINETIC-ANALYSIS OF ISCHEMIA-DAMAGED HEART-MITOCHONDRIA -WHICH PARTS OF THE OXIDATIVE-PHOSPHORYLATION SYSTEM ARE AFFECTED BY ISCHEMIA

We investigated the effects of ischemia on the kinetics and control of mitochondria isolated from normal and ischemic heart. The dependence of the respiratory chain, phosphorylation system and proton leak on th e mitochondrial membrane potential were measured in mitochondria from hearts after 0, 30 min and 45 min of in vitro ischemia. Data showed th at during the development of ischemia from the reversible (30 min) to the irreversible (45 min) phase, a progressive decrease in activity of the respiratory chain occurs. At the same time an increase in proton leak across the mitochondrial inner membrane was observed. Phosphoryla tion is inhibited but seems to be less affected by ischemia than respi ratory chain or proton leak. Control coefficients of the 3 blocks of r eactions over respiration rate were determined in different respirator y states between state 3 and state 3. Ischemia caused the control exer ted by the proton leak to increase in state 3 and the intermediate sta te and caused the control by the phosphorylation system to decrease in the intermediate state. Taken together, these results indicate that t he main effects of ischemia on mitochondrial respiration an an inhibit ion of the respiratory chain and an increase of the proton leak.