Injury of mitochondrial respiration and membrane potential during iron/ascorbate-induced peroxidation.

First functional events during peroxidation in mitochondria consisted in a progressive inhibition of the phosphorylating and uncoupled respiration with succinate and glutamate/malate as substrates, whereas the resting state respiration during the same period was virtually not influenced. The membrane potential registered at a time with the respiration rates was capable of being built up for a relatively long time interval with only minor decreases, and broke down rather promptly when the active respiration was highly diminished. Inhibition of respiration proceeded mainly during the initiation phase of peroxidation. Lag phases of varied length, of malondialdehyde formation which were predominantly attributed to the iron/protein ratios correlated closely with different time intervals needed to attain maximal inhibition of respiration and decrease in glutathione. Hence, the lessening of respiration, drop of membrane potential and loss of the antioxidant, glutathione, represent early stages in the causal chain of events which precede the onset of intensive lipid peroxidation.