Hepcidin and Ferroportin: The New Players in Iron Metabolism
Open accessAbstract
Systemic iron homeostasis is regulated by the interaction of the peptide hormone, hepcidin and the iron exporter, ferroportin. Mutations in FPN1, the gene that encodes ferroportin, result in iron-overload disease that shows dominant inheritance and variation in phenotype. The inheritance of ferroportin-linked disorders can be explained by the finding that ferroportin is a multimer and the product of the mutant allele participates in multimer formation. The nature of the ferroportin mutant can explain the variation in phenotype, which is due to either decreased iron export activity or decreased ability to be downregulated by hepcidin. Iron export through ferroportin is determined by the concentration of ferroportin in plasma membrane, which is the result of both synthetic and degradation events. Ferroportin degradation can occur by hepcidin-dependent and hepcidin-independent internalization. Ferroportin expression is regulated transcriptionally and posttranslationally.
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Hepcidin limits cellular iron efflux by binding to ferroportin and facilitating its internalization and ultimate degradation.
“It limits the cellular iron efflux by binding to FPN and facilitates its internalization and ultimate degradation [14].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [14]
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- Authors
- De Domenico, I., Ward, D., & Kaplan, J.
- Affiliations
- University of Utah (US)
- Venue
- Seminars in Liver Disease
- Publisher
- Georg Thieme Verlag KG
- Published
- 2011-08
- Volume
- 31
- Issue
- 03
- Pages
- 272-279
- ISSN
- 0272-8087 (ISSN-L)
- 1098-8971
- PMC
- PMC3706197
- OpenAlex
- W1999761445
- Cited by
- 71
- References
- 61
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 11 · 2014: 9 · 2013: 4 · 2012: 3
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Seminars in Liver Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK090257, DK070947, R01DK090257, R01DK070947)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, ferroportin, iron homeostasis, iron overload, iron export, transcriptional regulation, post-translational regulation
- MeSH terms
- Ferroportin, Animals, Gene Expression Regulation, Humans, Iron, Antimicrobial Cationic Peptides, Cation Transport Proteins, Hepcidins
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