Formation of phosphatidic acid in stressed mitochondria

Mitochondria are an important intracellular source of ROS as well as a sensitive target for oxidative damage Under certain pathological conditions such as iron or copper overload. Mitochondrial membranes are rich in the tetraacyl phospholipid cardiolipin. Its integrity is important for efficient oxidative phosphorylation. Mouse liver mitochondria were subjected to oxidative stress by the CL2+(Fe2+)/H2O2/ascorbate system. Phosphatidic acid was detected in oxidized mitochondria, but not in unperturbed mitochondria. The Cu2+/H2O2/and (or not) ascorbate system caused the formation of phosphatidic acid and phosphatidylhydroxyaceton e in cardiolipin liposomes. These products proceed via an HO-radical induced fragmentation taking place in the polar moiety of cardiolipin. Mass spectrometry analysis of phosphatidic acid newly formed in mitochondria revealed that it has been derived from fragmentation of cardiolipin. free-radical fragmentation of cardiolipin in its polar part with the formation of phosphatidic acid is Thus, a likely mechanism that damages mitochondria under conditions of oxidative stress. (C) 2008 Elsevier Inc. All rights reserved.