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New insights into the links between hypoxia and iron homeostasis

Authors
  • Renassia, Cyril1, 2, 3, 4
  • Peyssonnaux, Carole1, 2, 3, 4
  • 1 Department Endocrinology Metabolism and Diabetes, INSERM U1016, Institut Cochin
  • 2 CNRS, UMR8104
  • 3 Université Paris Descartes, Sorbonne Paris Cité
  • 4 Laboratory of Excellence GR-Ex, Paris, France
Type
Published Article
Journal
Current Opinion in Hematology
Publisher
Lippincott Williams And Wilkins
Publication Date
Apr 04, 2019
Volume
26
Issue
3
Pages
125–130
Identifiers
DOI: 10.1097/MOH.0000000000000494
PMID: 30855332
PMCID: PMC6467554
Source
PubMed Central
Keywords
License
Green

Abstract

Purpose of review This review outlines recent discoveries on the crosstalk between oxygen metabolism and iron homeostasis, focusing on the role of HIF-2 (hypoxia inducible factor-2) in the regulation of iron metabolism under physiopathological conditions. Recent findings The importance of the hepcidin/ferroportin axis in the modulation of intestinal HIF-2 to regulate iron absorption has been recently highlighted. Latest advances also reveal a direct titration of the bone morphogenetic proteins by the erythroferrone contributing to liver hepcidin suppression to increase iron availability. Iron is recycled thanks to erythrophagocytosis of senescent erythrocytes by macrophages. Hemolysis is frequent in sickle cell anemia, leading to increased erythrophagocytosis responsible of the macrophage polarization shift. New findings assessed the effects of hemolysis on macrophage polarization in the tumor microenvironment. Summary Hypoxia signaling links erythropoiesis with iron homeostasis. The use of HIF stabilizing or inhibiting drugs are promising therapeutic approaches in iron-associated diseases.

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