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

Authors
Tyurina-YY; Tungekar-MA; Jung-M-Y; Tyurin-VA; Greenberger-JS; Stoyanovsky-DA; Kagan-VE
Source
FEBS Lett 2012 Feb; 586(3):235-241
NIOSHTIC No.
20040484
Abstract
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.
Keywords
Antigens; Cell-biology; Cell-function; Cellular-function; Lipids; Author Keywords: Cardiolipin; Apoptosis; Mitochondria; Cardiolipin remodeling; Cardiolipin oxidation; Mitochondria-targeted triphenylphosphonium oleic acid ester
Contact
Yulia Y. Tyurina, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219
CODEN
FEBLAL
Publication Date
20120201
Document Type
Journal Article
Email Address
yyt1@pitt.edu
Funding Type
Grant
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282; B03282012
Issue of Publication
3
ISSN
0014-5793
Source Name
Federation of European Biochemical Societies Letters
State
PA
Performing Organization
University of Pittsburgh at Pittsburgh
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