The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Functional properties of human ferroportin, a cellular iron exporter reactive also with cobalt and zinc
Open accessAbstract
Iron homeostasis is achieved by regulating the intestinal absorption of the metal and its recycling by macrophages. Iron export from enterocytes or macrophages to blood plasma is thought to be mediated by ferroportin under the control of hepcidin. Although ferroportin was identified over a decade ago, little is understood about how it works. We expressed in Xenopus oocytes a human ferroportin-enhanced green fluorescent protein fusion protein and observed using confocal microscopy its exclusive plasma-membrane localization. As a first step in its characterization, we established an assay to detect functional expression of ferroportin by microinjecting oocytes with 55 Fe and measuring efflux. Ferroportin expression increased the first-order rate constants describing 55 Fe efflux up to 300-fold over control. Ferroportin-mediated 55 Fe efflux was saturable, temperature-dependent (activation energy, E a ≈ 17 kcal/mol), maximal at extracellular pH ≈ 7.5, and inactivated at extracellular pH < 6.0. We estimated that ferroportin reacts with iron at its intracellular aspect with apparent affinity constant < 10 −7 M. Ferroportin expression also stimulated efflux of 65 Zn and 57 Co but not of 64 Cu, 109 Cd, or 54 Mn. Hepcidin treatment of oocytes inhibited efflux of 55 Fe, 65 Zn, and 57 Co. Whereas hepcidin administration in mice resulted in a marked hypoferremia within 4 h, we observed no effect on serum zinc levels in those same animals. We conclude that ferroportin is an iron-preferring cellular metal-efflux transporter with a narrow substrate profile that includes cobalt and zinc. Whereas hepcidin strongly regulated serum iron levels in the mouse, we found no evidence that ferroportin plays an important role in zinc homeostasis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The exported species is almost certainly ferrous iron [12] but the energetics of iron export is not yet well characterized.”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [12]
In the citing paper
“The smaller ion Mn 2+ was previously found not to be effluxed by FPN in oocytes 83 , but appears to be transported in liposomes.”
From Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms (2020) · cites this paper as [83]
Citations
Cites
Lodish, H. F. (1986) · Cited by 5,650
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
Self-citationNemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420945 · Cited by 2,650
Self-citationPositional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422
The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis
Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., & Andrews, N. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.01.003 · Cited by 1,275
A Novel Mammalian Iron-regulated Protein Involved in Intracellular Iron Metabolism
Abboud, S., & Haile, D. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000713200 · Cited by 1,267
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122
Self-citationTransport and Diffusion Across Cell Membranes
Stein, W. D., & Lieb, W. R. (1986) · Elsevier eBooks · doi:10.1016/b978-0-12-664660-3.x5001-7 · Cited by 1,029
Regulation of Iron Metabolism by Hepcidin
Nemeth, E., & Ganz, T. (2006) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.26.061505.111303 · Cited by 756
Self-citation
Research works printed but not linked: 1
- Nemeth E, 2006, Haematologica, 91, 727
Cited by
Sorted by citations
Drakesmith, H., Nemeth, E., & Ganz, T. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.006 · Cited by 638
Self-citationManganese Is Essential for Neuronal Health
Horning, K. J., Caito, S. W., Tipps, K. G., Bowman, A. B., & Aschner, M. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071714-034419 · Cited by 623
Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis
Nemeth, E., & Ganz, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126493 · Cited by 540
“The exported species is almost certainly ferrous iron [12] but the energetics of iron export is not yet well characterized.”
BackgroundSelf-citationStructure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms
Billesbølle, C. B., Azumaya, C. M., Kretsch, R. C., Powers, A. S., Gonen, S., Schneider, S., Arvedson, T., Dror, R. O., Cheng, Y., & Manglik, A. (2020) · Nature · doi:10.1038/s41586-020-2668-z · Cited by 344
Dietary Cadmium Intake and Its Effects on Kidneys
Satarug, S. (2018) · Toxics · doi:10.3390/toxics6010015 · Cited by 347
Metadata
- Authors
- Mitchell, C. J., Shawki, A., Ganz, T., Nemeth, E., & Mackenzie, B.
- Affiliations
- University of Cincinnati (US)
- University of California, Los Angeles (US)
- Corresponding author
- Mackenzie, Bryan
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2014-03-01
- Volume
- 306
- Issue
- 5
- Pages
- C450-C459
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- PMC
- PMC4042619
- OpenAlex
- W2068355995
- Cited by
- 132
- References
- 54
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 8 · 2020: 14 · 2019: 11 · 2018: 16 · 2017: 16 · 2016: 7 · 2015: 9 · 2014: 5
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK08271, R01DK080047, P30DK078392)
- David Geffen School of Medicine, University of California, Los Angeles
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- ferroportin, iron efflux, metal transporters, iron homeostasis, hepcidin, zinc efflux, plasma membrane localization, substrate specificity, hypoferremia, zinc homeostasis
- MeSH terms
- Ferroportin, Animals, Biological Transport, Cell Membrane, Cobalt, Homeostasis, Humans, Hydrogen-Ion Concentration, Iron, Kinetics, Male, Mice, Inbred C57BL, Protein Binding, Recombinant Fusion Proteins, Temperature, Xenopus laevis, Zinc, Genes, Reporter, Microscopy, Confocal, Cation Transport Proteins, Green Fluorescent Proteins, Mice, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
