Mitochondria targeting of non-peroxidizable triphenylphosphonium conjugated oleic acid protects mouse embryonic cells against apoptosis: Role of cardiolipin remodeling

Details

• Alternative Title:
  FEBS Lett
• Personal Author:
  Tyurina, Yulia Y. ; Tungekar, Muhammad A. ; Jung, Mi-Yeon ; Tyurin, Vladimir A. ; Greenberger, Joel S. ; Stoyanovsky, Detcho A. ; Kagan, Valerian E.
• Description:
  Peroxidation of cardiolipin in mitochondria is essential for the execution of apoptosis. We suggested that integration of oleic acid into cardiolipin generates non-oxidizable cardiolipin species hence protects cells against apoptosis. We synthesized mitochondria-targeted triphenylphosphonium oleic acid ester. Using lipidomics analysis we found that pretreatment of mouse embryonic cells with triphenylphosphonium oleic acid ester resulted in decreased contents of polyunsaturated cardiolipins and elevation of its species containing oleic acid residues. This caused suppression of apoptosis induced by actinomycin D. Triacsin C, an inhibitor of acyl-CoA synthase, blocked integration of oleic acid into cardiolipin and restored cell sensitivity to apoptosis.
• Subjects:
  Animals Apoptosis Cardiolipins Cell Line Cytoprotection Dactinomycin Embryo, Mammalian Mice Mitochondria Oleic Acids Organophosphorus Compounds Oxidation-Reduction Triazenes

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• Source:
  FEBS Lett. 2011; 586(3):235-241.
• Pubmed ID:
  22210054
• Pubmed Central ID:
  PMC3273856
• Document Type:
  Journal Article
• Funding:
  ES020693/ES/NIEHS NIH HHS/United States ; HL094488/HL/NHLBI NIH HHS/United States ; HL70755/HL/NHLBI NIH HHS/United States ; OH008282/OH/NIOSH CDC HHS/United States ; R01 ES020693/ES/NIEHS NIH HHS/United States ; R01 ES020693-01/ES/NIEHS NIH HHS/United States ; R01 HL070755/HL/NHLBI NIH HHS/United States ; R01 HL070755-07/HL/NHLBI NIH HHS/United States ; R01 HL070755-08/HL/NHLBI NIH HHS/United States ; R01 HL094488/HL/NHLBI NIH HHS/United States ; R01 HL094488-02/HL/NHLBI NIH HHS/United States ; U19 AI068021/AI/NIAID NIH HHS/United States ; U19 AI068021-07/AI/NIAID NIH HHS/United States ; U19 AI068021-08/AI/NIAID NIH HHS/United States ; U19AIO68021/PHS HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States
• Volume:
  586
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:be94387f4d46bfb7180a1a0c7016c0fecdfa310e21649d692396839cb99e9b83
• Download URL:
  https://stacks.cdc.gov/view/cdc/33304/cdc_33304_DS1.pdf
• File Type:
  [PDF - 897.92 KB ]