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Ferroptosis and necroinflammation, a yet poorly explored link.

Cell Death Differ. 26, 14-24 (2019)
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Ferroptosis is a non-apoptotic form of cell death characterized by overwhelming iron-dependent lipid peroxidation, which contributes to a number of pathologies, most notably tissue ischemia/reperfusion injury, neurodegeneration and cancer. Cysteine availability, glutathione biosynthesis, polyunsaturated fatty acid metabolism and modulation of the phospholipidome are the key events of this necrotic cell death pathway. Non-enzymatic and enzymatic lipoxygenase (LOX)mediated lipid peroxidation of lipid bilayers is efficiently counteracted by the glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis. Preliminary studies suggest that bursting ferroptotic cells release pro-inflammatory damage-associated molecular patterns (DAMPs) that trigger the innate immune system as exemplified by diseased kidney and brain tissues where ferroptosis contributes to organ demise in a predominant manner. The GSH/GPX4 node is known to control the activities of LOX and prostaglandin-endoperoxide synthase (PTGS) via the so-called peroxide tone. Since LOX and PTGS products do have pro-and anti-inflammatory effects, one may speculate that these enzymes contribute to the ferroptotic process on several levels in cell-autonomous and non-autonomous ways. Hence, this review provides the reader with an outline on what is currently known about the link between ferroptosis and necroinflammation and discusses critical events that may alert the innate immune system in early phases when cells become sensitized towards ferroptosis.
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Publication type Article: Journal article
Document type Review
Keywords Glutathione-peroxidase 4; Regulated Cell-death; Cancer-cells; Lipid-peroxidation; Hydroperoxide; 12/15-lipoxygenase; Inhibition; Cystine; Lipoxygenases; Metabolism
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Quellenangaben Volume: 26, Issue: 1, Pages: 14-24 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed