mitochondrial pathway for biosynthesis of lipid mediators

Details

• Alternative Title:
  Nat Chem
• Personal Author:
  Tyurina, Yulia Y. ; Poloyac, Samuel M. ; Tyurin, Vladimir A. ; Kapralov, Alexander A. ; Jiang, Jianfei ; Anthonymuthu, Tamil Selvan ; Kapralova, Valentina I. ; Vikulina, Anna S. ; Jung, Mi-Yeon ; Epperly, Michael W. ; Mohammadyani, Dariush ; Klein-Seetharaman, Judith ; Jackson, Travis C. ; Kochanek, Patrick M. ; Pitt, Bruce R. ; Greenberger, Joel S. ; Vladimirov, Yury A. ; Bayır, Hülya ; Kagan, Valerian E.
• Description:
  The central role of mitochondria in metabolic pathways and in cell-death mechanisms requires sophisticated signalling systems. Essential in this signalling process is an array of lipid mediators derived from polyunsaturated fatty acids. However, the molecular machinery for the production of oxygenated polyunsaturated fatty acids is localized in the cytosol and their biosynthesis has not been identified in mitochondria. Here we report that a range of diversified polyunsaturated molecular species derived from a mitochondria-specific phospholipid, cardiolipin (CL), is oxidized by the intermembrane-space haemoprotein, cytochrome c. We show that a number of oxygenated CL species undergo phospholipase A2-catalysed hydrolysis and thus generate multiple oxygenated fatty acids, including well-known lipid mediators. This represents a new biosynthetic pathway for lipid mediators. We demonstrate that this pathway, which includes the oxidation of polyunsaturated CLs and accumulation of their hydrolysis products (oxygenated linoleic, arachidonic acids and monolysocardiolipins), is activated in vivo after acute tissue injury.
• Keywords:
  Animals Brain Calcium Cardiolipins Chromatography, Liquid Cytochromes C Fatty Acids, Unsaturated Female Group IV Phospholipases A2 Hydrogen Peroxide Intestine, Small Lysophospholipids Mice Mice, Inbred C57BL Mitochondria Oxidants Oxidation-Reduction Rats Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Whole-Body Irradiation

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• Source:
  Nat Chem. 6(6):542-552
• Pubmed ID:
  24848241
• Pubmed Central ID:
  PMC4201180
• Document Type:
  Journal Article
• Funding:
  R01 NS052315/NS/NINDS NIH HHSUnited States/ ; R01 OH008282/OH/NIOSH CDC HHSUnited States/ ; ES021068/ES/NIEHS NIH HHSUnited States/ ; R01 NS076511/NS/NINDS NIH HHSUnited States/ ; ES020693/ES/NIEHS NIH HHSUnited States/ ; NS076511/NS/NINDS NIH HHSUnited States/ ; P01 HL114453/HL/NHLBI NIH HHSUnited States/ ; R21 ES021068/ES/NIEHS NIH HHSUnited States/ ; S10RR023461/RR/NCRR NIH HHSUnited States/ ; R01 CA165065/CA/NCI NIH HHSUnited States/ ; UL1 TR000005/TR/NCATS NIH HHSUnited States/ ; NS061817/NS/NINDS NIH HHSUnited States/ ; R01 ES020693/ES/NIEHS NIH HHSUnited States/ ; U19 AI068021/AI/NIAID NIH HHSUnited States/ ; NS052315/NS/NINDS NIH HHSUnited States/ ; R37 NS061817/NS/NINDS NIH HHSUnited States/ ; S10 RR023461/RR/NCRR NIH HHSUnited States/ ; OH008282/OH/NIOSH CDC HHSUnited States/ ; R01 NS061817/NS/NINDS NIH HHSUnited States/
• Volume:
  6
• Issue:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:129229785bb730700a2e30043893cb6ace84def8fc5f75b1520b59de17891496
• Download URL:
  https://stacks.cdc.gov/view/cdc/27883/cdc_27883_DS1.pdf
• File Type:
  [PDF - 2.50 MB ]