Cited by 187Erythropoietin and Anemia TreatmentIron Metabolism and DisordersHemoglobin structure and function

Hypoxia-inducible factors link iron homeostasis and erythropoiesis

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Shah, Yatrik M., Xie, Liwei·2014·Gastroenterology

Abstract

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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Crossref · 10.1053/j.gastro.2013.12.031

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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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Research works printed but not linked: 2

  1. [27]27. Ivan M, Kondo K, Yang H, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: im- plications for O2 sensing. Science 2001;292:464-468.
  2. [37]37. Iyer NV, Kotch LE, Agani F, et al. Cellular and develop- mental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 1998;12:149-162.

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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)
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
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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