Journal Article

PreJuSER-7755

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Heterolytic reduction of fatty acid hydroperoxides by cytochrome c/cardiolipin complexes: antioxidant function in mitochondria

Belikova, N. A. ; Tyurina, Y. Y. ; Borisenko, G. ; Tyurin, V. ; Samhan Arias, A. K. ; Yanamala, N. ; Furtmüller, P. G. ; Klein-Seetharaman, J.FZJ* ; Obinger, C. ; Kagan, V. E.

2009
American Chemical Society Washington, DC

This record in other databases:      

Please use a persistent id in citations: doi:10.1021/ja904343c

Abstract: 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.

Keyword(s): Animals (MeSH) ; Antioxidants: metabolism (MeSH) ; Armoracia: enzymology (MeSH) ; Cardiolipins: metabolism (MeSH) ; Cytochromes c: metabolism (MeSH) ; Fatty Acids: metabolism (MeSH) ; Hydrogen Peroxide: metabolism (MeSH) ; Mitochondria, Liver: enzymology (MeSH) ; Models, Molecular (MeSH) ; Murinae (MeSH) ; Oxidation-Reduction (MeSH) ; Protein Binding (MeSH) ; Antioxidants ; Cardiolipins ; Fatty Acids ; Hydrogen Peroxide ; Cytochromes c ; J

Note: 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.).

---

Contributing Institute(s):

1. Molekulare Biophysik (ISB-2)

Research Program(s):

1. Programm Biosoft (N03)

Appears in the scientific report 2009

---