ArticleBlood2020
NCOA4 is regulated by HIF and mediates mobilization of murine hepatic iron stores after blood loss.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Ferroptosis in gouty arthritis: a potential therapeutic strategy.Frontiers in immunology · 2026Pooled it
- SUV39H2-mediated NCOA4 methylation controls ferritinophagy and ferroptosis in triple-negative breast cancer.Cell death & disease · 2026Article
- A hub for an herb: is STAT3 blockade at the epicenter of toosendanin-induced NCOA4-dependent ferritinophagy and ferroptosis in cancer cells?Journal of gastrointestinal oncology · 2026Article
- Unveiling melatonin's multifaceted actions against ferroptotic neurotoxicity in ischemic stroke.Toxicology reports · 2026Review
- Implications of ferritinophagy in cardiovascular diseases and its pharmacological modulation: underlying mechanisms and clinical translation strategies.Cellular & molecular biology letters · 2026Review
- FAM96A functions as a novel pace controller for iron uptake to maintain iron homeostasis and erythropoiesis.Cell death and differentiation · 2026Article
- Ferritinophagy: molecular mechanisms and its crosstalk with ferroptosis in chronic respiratory diseases.Cell biology and toxicology · 2026Review
- NCOA4 as a regulatory switch linking DNA damage to lipid peroxidation in radiation response.Frontiers in cell and developmental biology · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Iron-Related Metabolic Targets in the Treatment of Osteosarcoma: Research Progress and Prospects.Biomedicines · 2025Review
- Ferritinophagy in cardiovascular diseases: mechanisms and potential therapy.Molecular and cellular biochemistry · 2025Review
- Ferritinophagy Loss Drives Mitochondrial Iron Import and Colorectal Tumorigenesis.Research square · 2025Article
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Targeting hypoxia-inducible factor-1 in a hypoxidative stress model protects retinal pigment epithelium cells from cell death and metabolic dysregulation.Cell death discovery · 2025Article
- The impact of YTHDF2-mediated NCOA4 methylation on myocardial ferroptosis.Apoptosis : an international journal on programmed cell death · 2025Article
- Iron Metabolism and Muscle Aging: Where Ferritinophagy Meets Mitochondrial Quality Control.Cells · 2025Review
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- Targeting ferroptosis for improved radiotherapy outcomes in HPV-negative head and neck squamous cell carcinoma.Molecular oncology · 2025Article
- Comparative proteomics of HepG2 cells reveals NGLY1 as an important regulator of ferroptosis resistance and iron uptake.PloS one · 2025Article
- The transcription factor PPARA mediates SIRT1 regulation of NCOR1 to protect damaged heart cells.Cardiovascular diagnosis and therapy · 2024Article
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8 authors at 1 institution in 1 country.
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Abstract
The mechanisms by which phlebotomy promotes the mobilization of hepatic iron stores are not well understood. NCOA4 (nuclear receptor coactivator 4) is a widely expressed intracellular protein previously shown to mediate the autophagic degradation of ferritin. Here, we investigate a local requirement for NCOA4 in the regulation of hepatic iron stores and examine mechanisms of NCOA4 regulation. Hepatocyte-targeted Ncoa4 knockdown in nonphlebotomized mice had only modest effects on hepatic ferritin subunit levels and nonheme iron concentration. After phlebotomy, mice with hepatocyte-targeted Ncoa4 knockdown exhibited anemia and hypoferremia similar to control mice with intact Ncoa4 regulation but showed a markedly impaired ability to lower hepatic ferritin subunit levels and hepatic nonheme iron concentration. This impaired hepatic response was observed even when dietary iron was limited. In both human and murine hepatoma cell lines, treatment with chemicals that stabilize hypoxia inducible factor (HIF), including desferrioxamine, cobalt chloride, and dimethyloxalylglycine, raised NCOA4 messenger RNA. This NCOA4 messenger RNA induction occurred within 3 hours, preceded a rise in NCOA4 protein, and was attenuated in the setting of dual HIF-1α and HIF-2α knockdown. In summary, we show for the first time that NCOA4 plays a local role in facilitating iron mobilization from the liver after blood loss and that HIF regulates NCOA4 expression in cells of hepatic origin. Because the prolyl hydroxylases that regulate HIF stability are oxygen- and iron-dependent enzymes, our findings suggest a novel mechanism by which hypoxia and iron deficiency may modulate NCOA4 expression to impact iron homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.