Mitochondrial redox opto-lipidomics reveals mono-oxygenated cardiolipins as pro-apoptotic death signals

Details

• Personal Author:
  Amoscato AA ; Bayir H ; Cheikhi A ; Huang Z ; Jiang J ; Kagan VE ; Kapralov AA ; Klein-Seetharaman J ; Maguire J ; Mao G ; Planas-Iglesias J ; Qu F ; St. Croix CM ; Tyurin VA ; Tyurina YY
• Description:
  While opto-genetics has proven to have tremendous value in revealing the functions of the macromolecular machinery in cells, it is not amenable to exploration of small molecules such as phospholipids (PLs). Here, we describe a redox opto-lipidomics approach based on a combination of high affinity light-sensitive ligands to specific PLs in mitochondria with LC-MS based redox lipidomics/bioinformatics analysis for the characterization of pro-apoptotic lipid signals. We identified the formation of mono-oxygenated derivatives of C18:2-containing cardiolipins (CLs) in mitochondria after the exposure of 10-nonylacridine orange bromide (NAO)-loaded cells to light. We ascertained that these signals emerge as an immediate opto-lipidomics response, but they decay long before the commencement of apoptotic cell death. We found that a protonophoric uncoupler caused depolarization of mitochondria and prevented the mitochondrial accumulation of NAO, inhibited the formation of C18:2-CL oxidation products and protected cells from death. Redox opto-lipidomics extends the power of opto-biologic protocols to studies of small PL molecules resilient to opto-genetic manipulations. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Lipids Occupational Health Safety
• Keywords:
  Bioinformatics Cell Death Cell Metabolism Cell Signaling Cellular Reactions Genetic Engineering Humans Light Emission Liquid Chromatography Mass Spectrometry Metabolism Molecular Signaling Molecular Structure Optics Oxidation Reduction Reactions Oxidative Metabolism Phospholipids

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• ISSN:
  1554-8929
• 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:
  11
• Issue:
  2
• NIOSHTIC Number:
  nn:20048873
• Citation:
  ACS Chem Biol 2016 Feb; 11(2):530-540
• Contact Point Address:
  Valerian E. Kagan, Center for Free Radical and Antioxidant Health, Departments of Environmental and Occupational Health, Center for Biological Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
• Email:
  kagan@pitt.edu
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  ACS Chemical Biology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0ae1ffe679b704fffb65b95372e8f45c7f413c0913e0854e4146b788b2c15deb7e005d1e4bd23e09a0b9161f997efbd8748dde74b397f887c5f5d9482eeb0a10
• Download URL:
  https://stacks.cdc.gov/view/cdc/203496/cdc_203496_DS1.pdf
• File Type:
  [PDF - 2.69 MB ]