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Cited by 132Iron Metabolism and DisordersTrace Elements in HealthPlant Micronutrient Interactions and Effects

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

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Mitchell, Colin J., Shawki, Ali, Ganz, Tomas, Nemeth, Elizabeta, Mackenzie, Bryan·2014·American Journal of Physiology-Cell Physiology
DOI 10.1152/ajpcell.00348.2013PMC PMC4042619
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Abstract

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.

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  1. Nemeth E, 2006, Haematologica, 91, 727

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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
ORCID
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
DOI
10.1152/ajpcell.00348.2013
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
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

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