ArticleBlood2022
Modulation of the HIF2α-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Revisiting Inherited Metabolic Diseases (IMDs) Through the Lens of Selective Autophagy.Journal of inherited metabolic disease · 2026Review
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- Identification and characterization of novel hepcidin mimetics that modulate ferroportin function.Blood red cells & iron · 2026Article
- Labile iron pool dynamics do not drive ferroptosis in colorectal cancer cells.The Journal of biological chemistry · 2026Article
- Vitamin B6 deficiency anemia resembles iron-deficiency anemia but does not activate intestinal HIF2⍺.Experimental hematology · 2026Article
- Ferritinophagy: molecular mechanisms and its crosstalk with ferroptosis in chronic respiratory diseases.Cell biology and toxicology · 2026Review
- Intestine-Specific Ferroportin Ablation Rescues from Systemic Iron Overload in Mice.Nutrients · 2026Article
- Review
- Regulating Ferroptosis in Leukemic Stem Cells: From Stemness Preservation to Targeted Differentiation Strategies.Stem cell reviews and reports · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Labile iron pool dynamics do not drive ferroptosis potentiation in colorectal cancer cells.bioRxiv : the preprint server for biology · 2025Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Iron-Mediated Regulation in Adipose Tissue: A Comprehensive Review of Metabolism and Physiological Effects.Current obesity reports · 2025Review
- Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.Current protein & peptide science · 2025Review
- Dietary Iron Absorption: Biochemical and Nutritional Aspects.Advances in experimental medicine and biology · 2025Review
- Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.Autophagy · 2024Article
- FOXO1-NCOA4 Axis Contributes to Cisplatin-Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Iron Absorption: Molecular and Pathophysiological Aspects.Metabolites · 2024Review
- Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
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12 authors at 2 institutions in 1 country.
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Abstract
Intestinal iron absorption is activated during increased systemic demand for iron. The best-studied example is iron deficiency anemia, which increases intestinal iron absorption. Interestingly, the intestinal response to anemia is very similar to that of iron overload disorders, as both the conditions activate a transcriptional program that leads to a hyperabsorption of iron via the transcription factor hypoxia-inducible factor 2α (HIF2α). However, pathways for selective targeting of intestine-mediated iron overload remain unknown. Nuclear receptor coactivator 4 (NCOA4) is a critical cargo receptor for autophagic breakdown of ferritin and the subsequent release of iron, in a process termed ferritinophagy. Our work demonstrates that NCOA4-mediated intestinal ferritinophagy is integrated into systemic iron demand via HIF2α. To demonstrate the importance of the intestinal HIF2α/ferritinophagy axis in systemic iron homeostasis, whole-body and intestine-specific NCOA4-/- mouse lines were generated and assessed. The analyses revealed that the intestinal and systemic response to iron deficiency was not altered after disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency.
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Registered trials
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.