Mitochondria targeting of non-peroxidizable triphenylphosphonium conjugated oleic acid protects mouse embryonic cells against apoptosis: role of cardiolipin remodeling |
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Authors: | Tyurina Yulia Y Tungekar Muhammad A Jung Mi-Yeon Tyurin Vladimir A Greenberger Joel S Stoyanovsky Detcho A Kagan Valerian E |
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Institution: | Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. yyt1@pitt.edu |
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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. |
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