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Lipid changes in mitochondria isolated from rat kidney after various periods of ischemia were analysed by thin-layer chromatography and gas-liquid chromatography. Free fatty acids were increased at 30 min and more so thereafter. Total phospholipid fatty acids decreased steadily. The proportion of diphosphatidylglycerol (cardiolipin) in the total phospholipid fraction decreased at 30 min, but the proportion of phosphatidylcholine and phosphatidylethanolamine in the total phospholipid fraction did not change until the irreversible phase of ischemic injury. We have shown that decrease of cardiolipin in mitochondrial membrane occurs early during ischemia, and only during the irreversible phase of ischemia are phosphatidylethanolamine and phosphatidylcholine broken down. It is postulated that these phenomena are due to activation of phospholipase in the mitochondrial membrane.

The loss of ability to synthesize adenosine triphosphate (ATP) by mitochondria in ischemic cells even in a favorable medium correlates with the loss of cell viability. The early lesion at the molecular level needs further investigation but appears to involve an increased permeability of the mitochondrial membrane possibly promoting proton leak and obviating oxidative phosphorylation. The nature of this leak could involve changes in phospholipid-protein interactions, especially since the early release of free fatty acids and changes in phospholipid composition occur.