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 Cu(2+)(Fe(2+))/H(2)O(2)/ascorbate system. Phosphatidic acid was detected in oxidized mitochondria, but not in unperturbed mitochondria. The Cu(2+)/H(2)O(2)/and (or not) ascorbate system caused the formation of phosphatidic acid and phosphatidylhydroxyacetone 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. Thus, free-radical fragmentation of cardiolipin in its polar part with the formation of phosphatidic acid is a likely mechanism that damages mitochondria under conditions of oxidative stress.
Research Institute for Physical Chemical Problems of Belarusian State University, Minsk, Belarus.
Irina L
IL
Yurkova
Franziska
F
Stuckert
Mikhail A
MA
Kisel
Oleg I
OI
Shadyro
Juergen
J
Arnhold
Dominik
D
Huster
D000818:Animals; D055592:Biophysical Phenomena; D002308:Cardiolipins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity; D008081:Liposomes; D008670:Metals / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D002308:Cardiolipins; D008081:Liposomes; D008670:Metals; D010712:Phosphatidic Acids; D017382:Reactive Oxygen Species; D007501:Iron