Mitochondria targeting of non-peroxidizable triphenylphosphonium conjugated oleic acid protects mouse embryonic cells against apoptosis: role of cardiolipin remodeling.
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.
Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. yyt1@pitt.edu
Yulia Y
YY
Tyurina
Muhammad A
MA
Tungekar
Mi-Yeon
MY
Jung
Vladimir A
VA
Tyurin
Joel S
JS
Greenberger
Detcho A
DA
Stoyanovsky
Valerian E
VE
Kagan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects*; D003609:Dactinomycin / Q000494:pharmacology; D004622:Embryo, Mammalian; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009829:Oleic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D014226:Triazenes / Q000494:pharmacology
D002308:Cardiolipins; D009829:Oleic Acids; D009943:Organophosphorus Compounds; D014226:Triazenes; D003609:Dactinomycin; C034613:triacsin C