%0 Journal Article
%A Belikova, N.A.
%A Tyurina, Y.Y.
%A Borisenko, G.
%A Tyurin, V.
%A Samhan Arias, A.K.
%A Yanamala, N.
%A Furtmüller, P.G.
%A Klein-Seetharaman, J.
%A Obinger, C.
%A Kagan, V.E.
%T Heterolytic reduction of fatty acid hydroperoxides by cytochrome c/cardiolipin complexes: antioxidant function in mitochondria
%J Journal of the American Chemical Society
%V 131
%@ 0002-7863
%C Washington, DC
%I American Chemical Society
%M PreJuSER-7755
%P 11288 - 11289
%D 2009
%Z This work was supported by grants from the NIH (U19-AI068021, HL70755, R03TW007320, 2RO1LM007994-05), the NSF (CC0449117), the PittGrid, and la Junta de Extremadura, Orden 2008050288 (A.K.S.A.).
%X Cytochrome c (cyt c), a mitochondrial intermembrane electron shuttle between complexes III and IV, can, upon binding with an anionic phospholipid, cardiolipin (CL), act as a peroxidase that catalyzes cardiolipin oxidation. H(2)O(2) was considered as a source of oxidative equivalents for this reaction, which is essential for programmed cell death. Here we report that peroxidase cyt c/CL complexes can utilize free fatty acid hydroperoxides (FFA-OOH) at exceptionally high rates that are approximately 3 orders of magnitude higher than for H(2)O(2). Similarly, peroxidase activity of murine liver mitochondria was high with FFA-OOH. Using EPR spin trapping and LC-MS techniques, we have demonstrated that cyt c/CL complexes split FFA-OOH predominantly via a heterolytic mechanism, yielding hydroxy-fatty acids, whereas H(2)O(2) (and tert-butyl hydroperoxide, t-BuOOH) undergo homolytic cleavage. Computer simulations have revealed that Arg(38) and His(33) are important for the heterolytic mechanism at potential FFA-OOH binding sites of cyt c (but not for H(2)O(2) or t-BuOOH). Regulation of FFA-OOH metabolism may be an important function of cyt c that is associated with elimination of toxic FFA-OOH and synthesis of physiologically active hydroxy-fatty acids in mitochondria.
%K Animals
%K Antioxidants: metabolism
%K Armoracia: enzymology
%K Cardiolipins: metabolism
%K Cytochromes c: metabolism
%K Fatty Acids: metabolism
%K Hydrogen Peroxide: metabolism
%K Mitochondria, Liver: enzymology
%K Models, Molecular
%K Murinae
%K Oxidation-Reduction
%K Protein Binding
%K Antioxidants (NLM Chemicals)
%K Cardiolipins (NLM Chemicals)
%K Fatty Acids (NLM Chemicals)
%K Hydrogen Peroxide (NLM Chemicals)
%K Cytochromes c (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:19627079
%U <Go to ISI:>//WOS:000269379200009
%R 10.1021/ja904343c
%U https://juser.fz-juelich.de/record/7755