Mitochondria targeting of non-peroxidizable triphenylphosphonium conjugated oleic acid protects mouse embryonic cells against apoptosis: role of cardiolipin remodeling.
Tyurina-YY; Tungekar-MA; Jung-M-Y; Tyurin-VA; Greenberger-JS; Stoyanovsky-DA; Kagan-VE
FEBS Lett 2012 Feb; 586(3):235-241
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.
Antigens; Cell-biology; Cell-function; Cellular-function; Lipids;
Author Keywords: Cardiolipin; Apoptosis; Mitochondria; Cardiolipin remodeling; Cardiolipin oxidation; Mitochondria-targeted triphenylphosphonium oleic acid ester
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
Federation of European Biochemical Societies Letters
University of Pittsburgh at Pittsburgh