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Ferritin uptake by human erythroid precursors is a regulated iron uptake pathway
Open accessAbstract
Iron delivery to mammalian cells is traditionally ascribed to diferric transferrin (Tf). We recently reported that human erythroid precursor cells possess specific membranes receptors that bind and internalize acid isoferritin. Here we show that ferritin uptake by these cells is highly regulated and that the internalized ferritin-iron is used for home synthesis and thus, this process could constitute a physiological pathway for iron assimilation. Ferritin was internalized by a specific, saturable process, distinct from the uptake of iron associated with albumin. Ferritin uptake downregulated transferrin-receptor expression, indicating that internalized ferritin-iron was recognized as an integral part of the cellular iron content. Ferritin receptor expression was coordinated to cell development and was tightly regulated by cellular iron status. Receptor abundance was increased by iron-depletion and decreased by iron-loading, while the affinity of the ferritin receptor for acid isoferritin remained nearly constant (kd = 4.1 +/- 0.5 x 10(-6) mol/L). Under all experimental conditions, ferritin- and transferrin-receptor expression was closely coordinated, suggesting that these pathways possess a common regulatory element. It is concluded that ferritin uptake by erythroid cells constitutes an iron uptake pathway in addition to the classical transferrin uptake pathway.
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“Yeast frataxin YFH1 interacts with the ISC-assembly complex composed of the scaffold protein Isu1 and the cysteine desulfurase Nfs1 in a ferrous iron–dependent manner (102), suggesting a role of YFH1 in ISC synthesis (Table 2).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [102]
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Metadata
- Authors
- Gelvan, D., Fibach, E., Meyron-Holtz, E., & Konijn, A.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Department of Human Nutrition, Hebrew University, Faculty of Medicine, Jerusalem, Israel.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1996-10-15
- Volume
- 88
- Issue
- 8
- Pages
- 3200-3207
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2175549206
- Cited by
- 62
- References
- 39
- Citations by year
- 2025: 2 · 2023: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 3 · 2013: 1 · 2012: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Cancer Association
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Materials Science › Metals and Alloys › Iron and Steelmaking Processes
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- ferritin uptake, erythroid precursors, transferrin receptor, iron absorption, iron homeostasis, transferrin, receptor internalization, iron depletion, erythropoiesis
- MeSH terms
- Apoferritins, Biological Transport, Cells, Cultured, Ferritins, Humans, Iron, Receptors, Cell Surface, Receptors, Transferrin, Down-Regulation, Erythroid Precursor Cells, Iron-Binding Proteins
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