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Kagan, V.E.* ; Mao, G.* ; Qu, F.* ; Friedmann Angeli, J.P.F. ; Doll, S. ; St. Croix, C.* ; Dar, H.H.* ; Liu, B.* ; Tyurin, V.A.* ; Ritov, V.B.* ; Kapralov, A.A.* ; Amoscato, A.A.* ; Jiang, J.* ; Anthonymuthu, T.* ; Mohammadyani, D.* ; Yang, Q.* ; Proneth, B. ; Klein-Seetharaman, J.* ; Watkins, S.* ; Bahar, I.* ; Greenberger, J.* ; Mallampalli, R.K.* ; Stockwell, B.R.* ; Tyurina, Y.Y.* ; Conrad, M. ; Bayir, H.*

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.

Nat. Chem. Biol. 13, 81-90 (2017)
Verlagsversion Forschungsdaten DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Enigmatic lipid peroxidation products have been claimed as the proximate executioners of ferroptosis-a specialized death program triggered by insufficiency of glutathione peroxidase 4 (GPX4). Using quantitative redox lipidomics, reverse genetics, bioinformatics and systems biology, we discovered that ferroptosis involves a highly organized oxygenation center, wherein oxidation in endoplasmic-reticulum-associated compartments occurs on only one class of phospholipids (phosphatidylethanolamines (PEs)) and is specific toward two fatty acyls-arachidonoyl (AA) and adrenoyl (AdA). Suppression of AA or AdA esterification into PE by genetic or pharmacological inhibition of acyl-CoA synthase 4 (ACSL4) acts as a specific antiferroptotic rescue pathway. Lipoxygenase (LOX) generates doubly and triply-oxygenated (15-hydroperoxy)-diacylated PE species, which act as death signals, and tocopherols and tocotrienols (vitamin E) suppress LOX and protect against ferroptosis, suggesting a homeostatic physiological role for vitamin E. This oxidative PE death pathway may also represent a target for drug discovery.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Glutathione-peroxidase 4; Vitamin-e Action; Lipid-peroxidation; Aminophospholipid Asymmetry; Molecular-basis; Death; Lipoxygenase; Oxidation; Hydroperoxides; Degeneration
ISSN (print) / ISBN 1552-4450
e-ISSN 1552-4469
Quellenangaben Band: 13, Heft: 1, Seiten: 81-90 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Basingstoke
Begutachtungsstatus Peer reviewed