ArticleBlood advances2020
A new role of glutathione peroxidase 4 during human erythroblast enucleation.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Redox Modulation of Erythropoiesis by Selenoproteins.Biological trace element research · 2026Review
- Glycine Alleviates HMolecular neurobiology · 2026Article
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- TP53 Expression Status Alters Hemoglobinization and Ferroptosis Sensitivity in K-562 Cells.International journal of molecular sciences · 2025Article
- Cell death signaling in human erythron: erythrocytes lose the complexity of cell death machinery upon maturation.Apoptosis : an international journal on programmed cell death · 2025Review
- The Impact of Sodium Selenite and Seleno-L-Methionine on Stress Erythropoiesis in a Murine Model of Hemolytic Anemia.The Journal of nutrition · 2025Article
- Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia.Nature communications · 2024Article
- Human-augmented large language model-driven selection of glutathione peroxidase 4 as a candidate blood transcriptional biomarker for circulating erythroid cells.Scientific reports · 2024Article
- Erythroblast enucleation at a glance.Journal of cell science · 2024Review
- Modulation of Antioxidant Enzyme Expression of In Vitro Culture-Derived Reticulocytes.Antioxidants (Basel, Switzerland) · 2024Article
- Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.Journal of the American Heart Association · 2024Article
- Nanoparticle Targeting in Chemo-Resistant Ovarian Cancer Reveals Dual Axis of Therapeutic Vulnerability Involving Cholesterol Uptake and Cell Redox Balance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024Article
- The interactions between ineffective erythropoiesis and ferroptosis in β-thalassemia.Frontiers in physiology · 2024Review
- HDAC6 regulates human erythroid differentiation through modulation of JAK2 signalling.Journal of cellular and molecular medicine · 2023Article
- Circulating hemopexin modulates anthracycline cardiac toxicity in patients and in mice.Science advances · 2022Article
- Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022Review
- Review
- Expression Silencing of Glutathione Peroxidase 4 in Mouse Erythroleukemia Cells Delays In Vitro Erythropoiesis.International journal of molecular sciences · 2021Article
- Multiple-ancestry genome-wide association study identifies 27 loci associated with measures of hemolysis following blood storage.The Journal of clinical investigation · 2021Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selenoprotein glutathione peroxidase 4 (GPX4), the only member of the glutathione peroxidase family able to directly reduce cell membrane-oxidized fatty acids and cholesterol, was recently identified as the central regulator of ferroptosis. GPX4 knockdown in mouse hematopoietic cells leads to hemolytic anemia and to increased spleen erythroid progenitor death. The role of GPX4 during human erythropoiesis is unknown. Using in vitro erythroid differentiation, we show here that GPX4-irreversible inhibition by 1S,3R-RSL3 (RSL3) and its short hairpin RNA-mediated knockdown strongly impaired enucleation in a ferroptosis-independent manner not restored by tocopherol or iron chelators. During enucleation, GPX4 localized with lipid rafts at the cleavage furrows between reticulocytes and pyrenocytes. Its inhibition impacted enucleation after nuclear condensation and polarization and was associated with a defect in lipid raft clustering (cholera toxin staining) and myosin-regulatory light-chain phosphorylation. Because selenoprotein translation and cholesterol synthesis share a common precursor, we investigated whether the enucleation defect could represent a compensatory mechanism favoring GPX4 synthesis at the expense of cholesterol, known to be abundant in lipid rafts. Lipidomics and filipin staining failed to show any quantitative difference in cholesterol content after RSL3 exposure. However, addition of cholesterol increased cholera toxin staining and myosin-regulatory light-chain phosphorylation, and improved enucleation despite GPX4 knockdown. In summary, we identified GPX4 as a new actor of human erythroid enucleation, independent of its function in ferroptosis control. We described its involvement in lipid raft organization required for contractile ring assembly and cytokinesis, leading in fine to nucleus extrusion.
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