A mitochondrial pathway for biosynthesis of lipid mediators

Details

• Personal Author:
  Anthonymuthu TS ; Bayir H ; Epperly MW ; Greenberger JS ; Jackson TC ; Jiang J ; Jung M-Y ; Kagan VE ; Kapralov AA ; Kapralova VI ; Klein-Seetharaman J ; Kochanek PM ; Mohammadyani D ; Pitt BR ; Poloyac SM ; Tyurin VA ; Tyurina YY ; Vikulina AS ; Vladimirov YA
• 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. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Energy Metabolism Laboratories Nervous System Occupational Health Safety
• Keywords:
  Brain-function Brain-matter Chemical-reactions Drugs Laboratory-animals Metabolism Oxidation Pharmacology
• ISSN:
  1755-4330
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  6
• Issue:
  6
• NIOSHTIC Number:
  nn:20044800
• Citation:
  Nat Chem 2014 Jun; 6(6):542-552
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Nature Chemistry
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5b00854887543b9f8a75dc47cd8183abd4fa5ac5e281691208c8c8cce6ffb29ca9177556df42aa11e4aca64921f521b02d7d77e579392dbd0527a1e508605564
• Download URL:
  https://stacks.cdc.gov/view/cdc/200426/cdc_200426_DS1.pdf
• File Type:
  [PDF - 1.92 MB ]