The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin
Open accessAbstract
Ferroportin (FPN) mediates iron export from cells; FPN mutations are associated with the iron overloading disorder hemochromatosis. Previously, we found that the A77D, V162del, and G490D mutations inhibited FPN activity, but that other disease-associated FPN variants retained full iron export capability. The peptide hormone hepcidin inhibits FPN as part of a homeostatic negative feedback loop. We measured surface expression and function of wild-type FPN and fully active FPN mutants in the presence of hepcidin. We found that the Y64N and C326Y mutants of FPN are completely resistant to hepcidin inhibition and that N144D and N144H are partially resistant. Hemochromatosis-associated FPN mutations, therefore, either reduce iron export ability or produce an FPN variant that is insensitive to hepcidin. The former mutation type is associated with Kupffer-cell iron deposition and normal transferrin saturation in vivo, whereas patients with the latter category of FPN mutation have high transferrin saturation and tend to deposit iron throughout the liver parenchyma. FPN-linked hemochromatosis may have a variable pathogenesis depending on the causative FPN mutant.
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In the citing paper
“Deficits in hepcidin-mediated regulation of FPN, often due to hereditary hemochromatoses, lead to iron overload and widespread tissue damage affecting the liver, heart, pancreas, and joints 11-13 .”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several hereditary hemochromatosis mutations in FPN directly coordinate Co 2+ in the C domain, including C326S/F/Y 13,29-31 and H507R 32 .”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several FPN mutations decrease hepcidin binding to FPN, including N144H/D/T 34-36 , C326S/F/Y 13,29-31 , Y333H 37 , Y501C 7,38 , D504N 7,39 and H507R 32 .”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [13]
Experimental — accuracy not yet measuredIn the citing paper
“It is essential to the development of these cell types as Spic −/− mice have drastically reduced numbers of RPM and EIM which lead to reduced proerythroblast numbers in the steady state, supporting the idea that iron recycling is essential to sustain iron-sufficient erythropoiesis [58].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [58]
In the citing paper
“Missense mutations that affected the subcellular localization or transporter function of ferroportin (”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [159]
In the citing paper
“In contrast, missense mutations that rendered ferroportin insensitive to regulation by hepcidin (”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [159]
In the citing paper
“These issues were resolved by the discovery that there are 2 broad categories of ferroportin mutations.158,159”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [159]
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Citations
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“…that this group of mutations may resist inhibition by hepcidin, so interfering with its homeostatic negative feedback loop and resulting in a permanently “turned on” iron exporter (Schimanski et al., 2005; Drakesmith et al., 2005). www.intechopen.com Relationship Between Iron and Erythropoiesis 71”
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Metadata
- Authors
- Drakesmith, H., Schimanski, L. M., Ormerod, E., Merryweather-Clarke, A. T., Viprakasit, V., Edwards, J. P., Sweetland, E., Bastin, J. M., Cowley, D., Chinthammitr, Y., Robson, K. J. H., & Townsend, A. R. M.
- Affiliations
- Siriraj Hospital (TH)
- From the Weatherall Institute of Molecular Medicine, Oxford, United Kingdom; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom; Department of Paediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; and Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-08-01
- Volume
- 106
- Issue
- 3
- Pages
- 1092-1097
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2131823953
- Cited by
- 264
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 14 · 2012: 11
- FWCI
- 15.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- ferroportin, hepcidin, hemochromatosis, iron export, iron overload, transferrin saturation, Kupffer cells, liver iron deposition, iron homeostasis
- MeSH terms
- Ferroportin, Cell Line, Drug Resistance, Gene Expression Regulation, Hemochromatosis, Humans, Iron, Iron Radioisotopes, Transferrin, Mutation, Missense, Antimicrobial Cationic Peptides, Cation Transport Proteins, Hepcidins
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