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Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors.

Blood 127, 139-148 (2016)
Publishers Version Postprint DOI PMC
Open Access Green
as soon as is submitted to ZB.
Maintaining cellular redox balance is vital for cell survival and tissue homoeostasis since imbalanced production of ROS may lead to oxidative stress and cell death. The anti-oxidant enzyme glutathione peroxidase 4 (Gpx4) is a key regulator of oxidative stress-induced cell death. We show that mice with deletion of Gpx4 in hematopoietic cells develop anemia and that it is essential for preventing RIP3 dependent necroptosis in erythroid precursor cells. Absence of Gpx4 leads to functional inactivation of caspase 8 by glutathionylation. This results in necroptosis, which occurs independently of TNFα activation. While genetic ablation of Rip3 normalizes reticulocyte maturation and prevents anemia, ROS accumulation and lipid peroxidation in Gpx4 deficient cells remain high. Our results demonstrate that ROS and lipid hydroperoxides function as so far unrecognized unconventional upstream signaling activators of RIP3-dependent necroptosis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gpx4 Is Essential For Preventing Anemia In Mice Via Inhibiting Rip3-dependent Necroptosis In Erythroid Precursor Cells ; Ros Accumulation And Lipid Peroxidation In Erythroid Precursor Cells Trigger Receptor-independent Activation Of Necroptosis; Tumor-necrosis-factor; Cell-death; Programmed Necrosis; Hydrogen-peroxide; Inflammation; Apoptosis; Mice; Homeostasis; Ferroptosis; Protects
Reviewing status