Iron-Sensing Proteins that Regulate Hepcidin and Enteric Iron Absorption
Abstract
The human body cannot actively excrete excess iron. As a consequence, iron absorption must be strictly regulated to ensure adequate iron uptake and prevent toxic iron accumulation. Iron absorption is controlled chiefly by hepcidin, the iron-regulatory hormone. Produced by the liver and secreted into the circulation, hepcidin regulates iron metabolism by inhibiting iron release from cells, including duodenal enterocytes, which mediate the absorption of dietary iron. Hepcidin production increases in response to iron loading and decreases in iron deficiency. Such regulation of hepcidin expression serves to modulate iron absorption to meet body iron demand. This review discusses the proteins that orchestrate hepatic hepcidin production and iron absorption by the intestine. Emphasis is placed on the proteins that directly sense iron and how they coordinate and fine-tune the molecular, cellular, and physiologic responses to iron deficiency and overload.
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Iron export from duodenal enterocytes, macrophages and hepatocytes through FPN1 appears to be a limiting step, modulated by hepcidin.
“Iron export from duodenal enterocytes, macrophages and hepatocytes through FPNI appears to be a limiting step, modulated by the peptide hormone, hepcidin.”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Knutson, 2010
Hepcidin expression is regulated by BMP and TfRII-dependent signaling pathways in response to extracellular and intracellular iron.
“Two main iron-related signaling pathways, one involving bone morphogenetic proteins (BMPs -these comprise a group of at least 20 soluble molecules belonging to the transforming growth factor β superfamily) and the other dependent on transferrin receptor II (TfRII) regulate hepcidin regulation.”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Knutson, 2010
Non-heme iron is taken up from the lumen via DMT1 and actively transported as Fe(II); dietary Fe(III) is reduced by DCytb prior to transport.
“Non-heme iron which comprises a major component of dietary iron is taken up from the lumen via the transmembrane protein divalent metal transporter (DMT1) located at the enterocyte apical membrane and actively transported as Fe (II) ion.”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Knutson, 2010
Binding of hepcidin to FPN1 triggers internalization and degradation of the receptor-ligand complex, ceasing cellular iron export.
“Binding of hepcidin to FPN1 triggers the internalization and degradation of the receptor-ligand complex.Once internalized, the hepcidin-FPN1 complex is degraded in lysosomes and cellular iron export ceases”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Knutson, 2010
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References 142 · Cited by 96
- Authors
- Knutson, M. D.
- Affiliations
- University of Florida (US)
- Corresponding author
- Knutson, Mitchell D.
- ORCID
- Knutson, Mitchell D.
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2010-07-01
- Volume
- 30
- Issue
- 1
- Pages
- 149-171
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W2119755122
- Cited by
- 96
- References
- 142
- Citations by year
- 2025: 1 · 2024: 11 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 13 · 2013: 13 · 2012: 9
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 080706)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- hepcidin, iron sensing, iron absorption, duodenal enterocytes, iron metabolism, iron deficiency, iron overload, iron regulatory hormone, iron regulatory proteins, intestinal iron absorption
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Intestinal Absorption, Iron, Liver, Signal Transduction, Iron Overload, Enterocytes, Antimicrobial Cationic Peptides, Hepcidins
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