Hypoxia-inducible factors link iron homeostasis and erythropoiesis
Open accessAbstract
Iron is required for efficient oxygen transport, and hypoxia signaling links erythropoiesis with iron homeostasis. Hypoxia induces a highly conserved signaling pathway in cells under conditions of low levels of O2. One component of this pathway, hypoxia-inducible factor (HIF), is a transcription factor that is highly active in hypoxic cells. The first HIF target gene characterized was EPO, which encodes erythropoietin-a glycoprotein hormone that controls erythropoiesis. In the past decade, there have been fundamental advances in our understanding of how hypoxia regulates iron levels to support erythropoiesis and maintain systemic iron homeostasis. We review the cell type-specific effects of hypoxia and HIFs in adaptive response to changes in oxygen and iron availability as well as potential uses of HIF modulators for patients with iron-related disorders.
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IRP1-mediated suppression of HIF-2α translation prevents HIF-2-mediated erythropoiesis under iron starvation.
“IRP1-mediated suppression of HIF-2α translation prevents HIF-2 mediated induction of erythropoiesis under iron starvation conditions, when the production of hemoglobin, an iron-containing molecule, may be limiting [23].”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [23]
The “Interactions Between IRP1 and HIF-2a” section (page not provided) reports that iron deficiency inhibits HIF-2α translation through IRP activity. It proposes that the IRP1–HIF-2α interaction could limit erythropoiesis under hypoxia and low systemic iron, but does not establish that it prevents erythropoiesis under iron starvation. (LLM, conf=0.86)
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- Authors
- Shah, Y. M., & Xie, L.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Shah, Yatrik M.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 146
- Issue
- 3
- Pages
- 630-642
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3943938
- OpenAlex
- W2168760727
- Cited by
- 187
- References
- 145
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 23 · 2023: 19 · 2022: 22 · 2021: 22 · 2020: 15 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 7 · 2015: 11 · 2014: 4
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- University of Michigan Comprehensive Cancer Center
- National Cancer Institute (CA148828, R01CA148828)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-095201, R01DK095201)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- hypoxia-inducible factor, iron homeostasis, erythropoiesis, erythropoietin, hypoxia signaling, oxygen availability
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Hypoxia, Erythropoiesis, Erythropoietin, Homeostasis, Humans, Iron, Liver, Oxygen, Signal Transduction, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1
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