Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals

Details

• Alternative Title:
  ACS Chem Biol
• Personal Author:
  Mao, Gaowei ; Qu, Feng ; St. Croix, Claudette M. ; Tyurina, Yulia Y. ; Planas-Iglesias, Joan ; Jiang, Jianfei ; Huang, Zhentai ; Amoscato, Andrew A. ; Tyurin, Vladimir A. ; Kapralov, Alexandr A. ; Cheikhi, Amin ; Maguire, John ; Klein-Seetharaman, Judith ; Bayır, Hülya ; Kagan, Valerian E.
• 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 product,s 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.
• Subjects:
  Acridine Orange Apoptosis Cardiolipins Coloring Agents Computational Biology HeLa Cells Humans Light Mitochondria Oxidation-Reduction Oxygen

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• Source:
  ACS Chem Biol. 11(2):530-540.
• Pubmed ID:
  26697918
• Pubmed Central ID:
  PMC5741079
• Document Type:
  Journal Article
• Funding:
  S10RR023461/RR/NCRR NIH HHS/United States ; R01 CA165065/CA/NCI NIH HHS/United States ; CA 165065/CA/NCI NIH HHS/United States ; NS061817/NS/NINDS NIH HHS/United States ; R01 ES020693/ES/NIEHS NIH HHS/United States ; R01 OH008282/OH/NIOSH CDC HHS/United States ; U19 AI068021/AI/NIAID NIH HHS/United States ; NS052315/NS/NINDS NIH HHS/United States ; U19AIO68021/PHS HHS/United States ; R01 NS076511/NS/NINDS NIH HHS/United States ; ES020693/ES/NIEHS NIH HHS/United States ; EB17268/EB/NIBIB NIH HHS/United States ; NS076511/NS/NINDS NIH HHS/United States ; OH008282/OH/NIOSH CDC HHS/United States ; R01 NS061817/NS/NINDS NIH HHS/United States ; P01 HL114453/HL/NHLBI NIH HHS/United States ; HL114453/HL/NHLBI NIH HHS/United States ; R21 ES021068/ES/NIEHS NIH HHS/United States
• Volume:
  11
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e3757a6b46d34fc605877407883eea16b72edc22667fd07e3c03fc72aa3ffac1
• Download URL:
  https://stacks.cdc.gov/view/cdc/50619/cdc_50619_DS1.pdf
• File Type:
  [PDF - 759.28 KB ]