Home LiteratureArticle Details
PMID: 19484405 Published · ppublish English Journal Article Review

Mammalian iron transport.

Cellular and molecular life sciences : CMLS ·Vol. 66 ·No. 20 ·2009-10-00 ·Pages 3241-61

Anderson GJ, Vulpe CD

Abstract

Iron is essential for basic cellular processes but is toxic when present in excess. Consequently, iron transport into and out of cells is tightly regulated. Most iron is delivered to cells bound to plasma transferrin via a process that involves transferrin receptor 1, divalent metal-ion transporter 1 and several other proteins. Non-transferrin-bound iron can also be taken up efficiently by cells, although the mechanism is poorly understood. Cells can divest themselves of iron via the iron export protein ferroportin in conjunction with an iron oxidase. The linking of an oxidoreductase to a membrane permease is a common theme in membrane iron transport. At the systemic level, iron transport is regulated by the liver-derived peptide hepcidin which acts on ferroportin to control iron release to the plasma.

MeSH Terms
Animals Antimicrobial Cationic Peptides/metabolism,physiology Biological Transport Carrier Proteins/genetics,metabolism,physiology Erythroid Cells/metabolism Gene Expression Regulation Hepatocytes/metabolism,physiology Hepcidins Homeostasis Iron/blood,metabolism Macrophages/metabolism,physiology Mammals/metabolism Mitochondria/metabolism Models, Biological Oxidoreductases/metabolism,physiology
Chemicals
Antimicrobial Cationic Peptides Carrier Proteins Hepcidins Iron Oxidoreductases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Anderson Gregory Jon
Iron Metabolism Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, QLD, Australia. Greg.Anderson@qimr.edu.au
Vulpe Christopher D
References (201)
201 references, click to expand
  1. Hepatic iron metabolism.
    Semin Liver Dis. 2005 Nov;25(4):420-32 PMID: 16315136
  2. Lack of the bone morphogenetic protein BMP6 induces massive iron overload.
    Nat Genet. 2009 Apr;41(4):478-81 PMID: 19252488
  3. Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver.
    J Clin Invest. 2005 May;115(5):1258-66 PMID: 15849611
  4. Crystal structure of the ectodomain of human transferrin receptor.
    Science. 1999 Oct 22;286(5440):779-82 PMID: 10531064
  5. Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter.
    J Mol Biol. 2009 Feb 27;386(3):717-32 PMID: 19150361
  6. Function and regulation of transferrin and ferritin.
    Semin Hematol. 1998 Jan;35(1):35-54 PMID: 9460808
  7. Friedreich ataxia.
    Semin Pediatr Neurol. 2003 Sep;10(3):163-72 PMID: 14653404
  8. The endocytosis of transferrin by rat intestinal epithelial cells.
    Gastroenterology. 1994 Feb;106(2):414-22 PMID: 8299907
  9. Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway.
    Mol Biol Cell. 2007 Mar;18(3):743-54 PMID: 17182845
  10. Inhibition of uptake of transferrin-bound iron by human hepatoma cells by nontransferrin-bound iron.
    Hepatology. 1997 Sep;26(3):691-8 PMID: 9303500
  11. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs).
    J Clin Invest. 2007 Jul;117(7):1926-32 PMID: 17557118
  12. Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis.
    Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2214-9 PMID: 10681454
  13. Characterization of non-transferrin-bound iron clearance by rat liver.
    J Biol Chem. 1986 Aug 15;261(23):10909-14 PMID: 3733737
  14. MDB: the Metalloprotein Database and Browser at The Scripps Research Institute.
    Nucleic Acids Res. 2002 Jan 1;30(1):379-82 PMID: 11752342
  15. Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system.
    J Biol Chem. 2003 Jul 18;278(29):27144-8 PMID: 12743117
  16. Steap proteins: implications for iron and copper metabolism.
    Nutr Rev. 2007 Jul;65(7):335-40 PMID: 17695374
  17. Uptake of iron from transferrin by isolated rat hepatocytes. A redox-mediated plasma membrane process?
    J Biol Chem. 1988 Jun 25;263(18):8844-50 PMID: 3379048
  18. Hepcidin--a regulator of intestinal iron absorption and iron recycling by macrophages.
    Best Pract Res Clin Haematol. 2005 Jun;18(2):171-82 PMID: 15737883
  19. The Steap proteins are metalloreductases.
    Blood. 2006 Aug 15;108(4):1388-94 PMID: 16609065
  20. Studies on familial hypotransferrinemia: unique clinical course and molecular pathology.
    Am J Hum Genet. 1993 Jul;53(1):201-13 PMID: 8317485
  21. Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression.
    Am J Physiol Gastrointest Liver Physiol. 2000 Nov;279(5):G1070-9 PMID: 11053005
  22. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin.
    EMBO J. 2007 Jun 20;26(12):2823-31 PMID: 17541408
  23. The role of ceruloplasmin in iron metabolism.
    J Clin Invest. 1970 Dec;49(12):2408-17 PMID: 5480864
  24. Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking.
    Genomics. 2005 Dec;86(6):668-73 PMID: 16289749
  25. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells.
    Nat Genet. 2005 Nov;37(11):1264-9 PMID: 16227996
  26. Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia.
    Blood. 2005 Feb 15;105(4):1797-802 PMID: 15479721
  27. Structure, topology and assembly of a 32-mer peptide corresponding to the loop 3 and transmembrane domain 4 of divalent metal transporter (DMT1) in membrane-mimetic environments.
    J Inorg Biochem. 2008 May-Jun;102(5-6):1257-66 PMID: 18243325
  28. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism.
    Nat Genet. 2009 Apr;41(4):482-7 PMID: 19252486
  29. The role of transporters in cellular heme and porphyrin homeostasis.
    Pharmacol Ther. 2007 Jun;114(3):345-58 PMID: 17368550
  30. Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae.
    Mol Cell Biol. 1990 May;10(5):2294-301 PMID: 2183029
  31. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.
    Nature. 2000 Feb 17;403(6771):776-81 PMID: 10693807
  32. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis.
    Nat Genet. 2003 Jan;33(1):21-2 PMID: 12469120
  33. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse.
    Nat Genet. 1999 Feb;21(2):195-9 PMID: 9988272
  34. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene.
    Nat Genet. 1997 Aug;16(4):383-6 PMID: 9241278
  35. The natural resistance-associated macrophage protein 1 Slc11a1 (formerly Nramp1) and iron metabolism in macrophages.
    Microbes Infect. 2002 Mar;4(3):351-9 PMID: 11909746
  36. Recent advances in mammalian haem transport.
    Trends Biochem Sci. 2006 Mar;31(3):182-8 PMID: 16487711
  37. Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation.
    J Biol Chem. 1999 Aug 20;274(34):24142-6 PMID: 10446187
  38. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin.
    Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4596-601 PMID: 11930010
  39. Iron accumulation in the liver of male patients with Wilson's disease.
    Am J Gastroenterol. 2001 Nov;96(11):3147-51 PMID: 11721763
  40. Haptoglobin: function and polymorphism.
    Clin Lab. 2000;46(11-12):547-52 PMID: 11109501
  41. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload.
    J Biol Chem. 2001 Mar 16;276(11):7811-9 PMID: 11113132
  42. Iron metabolism in the hemoglobin-deficit mouse: correlation of diferric transferrin with hepcidin expression.
    Blood. 2006 Feb 15;107(4):1659-64 PMID: 16239432
  43. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family.
    J Biol Chem. 1999 Jul 23;274(30):20826-32 PMID: 10409623
  44. Transferrin receptor 1.
    Int J Biochem Cell Biol. 2004 Nov;36(11):2137-43 PMID: 15313461
  45. Decreased liver hepcidin expression in the Hfe knockout mouse.
    Blood Cells Mol Dis. 2002 Nov-Dec;29(3):361-6 PMID: 12547226
  46. Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms.
    Annu Rev Cell Dev Biol. 2006;22:457-86 PMID: 16824008
  47. CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response.
    Ann Med. 2004;36(5):347-54 PMID: 15478309
  48. The mechanisms of iron uptake by fetal rat hepatocytes in culture.
    Hepatology. 1986 Sep-Oct;6(5):852-8 PMID: 3758939
  49. The heme oxygenase system: update 2005.
    Antioxid Redox Signal. 2005 Nov-Dec;7(11-12):1761-6 PMID: 16356137
  50. Diminished acquisition of iron by reticulocytes from mice with hemoglobin deficit.
    Exp Hematol. 1987 Jul;15(6):671-5 PMID: 3595766
  51. UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis.
    Blood. 2003 Apr 15;101(8):3288-93 PMID: 12480712
  52. Divalent metal transporter 1.
    Hematology. 2005 Aug;10(4):339-45 PMID: 16085548
  53. Evidence for the multimeric structure of ferroportin.
    Blood. 2007 Mar 1;109(5):2205-9 PMID: 17077321
  54. Ceruloplasmin metabolism and function.
    Annu Rev Nutr. 2002;22:439-58 PMID: 12055353
  55. A novel mammalian iron-regulated protein involved in intracellular iron metabolism.
    J Biol Chem. 2000 Jun 30;275(26):19906-12 PMID: 10747949
  56. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis.
    Lancet. 2003 Feb 22;361(9358):669-73 PMID: 12606179
  57. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression.
    Nat Genet. 2006 May;38(5):531-9 PMID: 16604073
  58. Unexpected role of ceruloplasmin in intestinal iron absorption.
    Cell Metab. 2005 Nov;2(5):309-19 PMID: 16271531
  59. Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells.
    J Biol Chem. 1993 Mar 15;268(8):5974-8 PMID: 8449958
  60. Hepcidin is decreased in TFR2 hemochromatosis.
    Blood. 2005 Feb 15;105(4):1803-6 PMID: 15486069
  61. Binding of apotransferrin to K562 cells: explanation of the transferrin cycle.
    Proc Natl Acad Sci U S A. 1983 Apr;80(8):2263-6 PMID: 6300904
  62. The role of transferrin in the mechanism of cellular iron uptake.
    Biochem J. 1990 Oct 1;271(1):1-9 PMID: 2222403
  63. An iron-regulated ferric reductase associated with the absorption of dietary iron.
    Science. 2001 Mar 2;291(5509):1755-9 PMID: 11230685
  64. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg.
    Cell. 1993 May 7;73(3):469-85 PMID: 8490962
  65. Anemia of the Belgrade rat: evidence for defective membrane transport of iron.
    Blood. 1987 Jul;70(1):38-44 PMID: 3593971
  66. Uptake and subcellular processing of 59Fe-125I-labelled transferrin by rat liver.
    Biochem J. 1986 Jul 1;237(1):163-73 PMID: 3800875
  67. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10653-8 PMID: 12134060
  68. Modification of iron regulation by the inflammatory response.
    Best Pract Res Clin Haematol. 2005 Jun;18(2):183-201 PMID: 15737884
  69. Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2).
    Blood. 2005 Oct 1;106(7):2580-9 PMID: 15956281
  70. Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2.
    Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3800-5 PMID: 19234114
  71. Iron-dependent regulation of the divalent metal ion transporter.
    FEBS Lett. 2001 Dec 7;509(2):309-16 PMID: 11741608
  72. Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD.
    Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2728-36 PMID: 18326691
  73. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis.
    EMBO J. 2004 Jan 28;23(2):386-95 PMID: 14726953
  74. Kinetic characterization of reductant dependent processes of iron mobilization from endocytic vesicles.
    Biochemistry. 1992 Jun 30;31(25):5820-30 PMID: 1535218
  75. Influence of parenteral iron preparations on non-transferrin bound iron uptake, the iron regulatory protein and the expression of ferritin and the divalent metal transporter DMT-1 in HepG2 human hepatoma cells.
    Biochem Pharmacol. 2003 Jun 15;65(12):1973-8 PMID: 12787877
  76. Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome.
    J Exp Med. 1997 Feb 17;185(4):717-30 PMID: 9034150
  77. Iron metabolism and the IRE/IRP regulatory system: an update.
    Ann N Y Acad Sci. 2004 Mar;1012:1-13 PMID: 15105251
  78. Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation antiporter.
    Biochem J. 2001 Mar 15;354(Pt 3):511-9 PMID: 11237855
  79. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8780-5 PMID: 11447267
  80. Site-directed mutagenesis investigation of coupling properties of metal ion transport by DCT1.
    Biochim Biophys Acta. 2008 Jan;1778(1):334-41 PMID: 17980698
  81. Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload.
    Gut. 2000 Feb;46(2):270-6 PMID: 10644324
  82. Increased susceptibility in Hp knockout mice during acute hemolysis.
    Blood. 1998 Sep 15;92(6):1870-7 PMID: 9731043
  83. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis.
    Nat Genet. 2004 Jan;36(1):77-82 PMID: 14647275
  84. The ferritins: molecular properties, iron storage function and cellular regulation.
    Biochim Biophys Acta. 1996 Jul 31;1275(3):161-203 PMID: 8695634
  85. Oxygen-binding haem proteins.
    Exp Physiol. 2008 Jan;93(1):128-32 PMID: 17981931
  86. Non-HFE hemochromatosis.
    Hepatology. 2004 Jan;39(1):21-9 PMID: 14752817
  87. Biosynthesis of heme in mammals.
    Biochim Biophys Acta. 2006 Jul;1763(7):723-36 PMID: 16839620
  88. Hepcidin: from discovery to differential diagnosis.
    Haematologica. 2008 Jan;93(1):90-7 PMID: 18166790
  89. Recent progress in structure-function analyses of Nramp proton-dependent metal-ion transporters.
    Biochem Cell Biol. 2006 Dec;84(6):960-78 PMID: 17215883
  90. Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice.
    Nat Genet. 2007 Aug;39(8):1025-32 PMID: 17632513
  91. Identification of an intestinal heme transporter.
    Cell. 2005 Sep 9;122(5):789-801 PMID: 16143108
  92. Transferrin receptor-independent uptake of differic transferrin by human hepatoma cells with antisense inhibition of receptor expression.
    Hepatology. 1996 Jun;23(6):1512-20 PMID: 8675172
  93. Mitoferrin is essential for erythroid iron assimilation.
    Nature. 2006 Mar 2;440(7080):96-100 PMID: 16511496
  94. Non-transferrin iron uptake by trophoblast cells in culture. Significance of a NADH-dependent ferrireductase.
    Placenta. 1998 Sep;19(7):525-30 PMID: 9778126
  95. Hemopexin: structure, function, and regulation.
    DNA Cell Biol. 2002 Apr;21(4):297-306 PMID: 12042069
  96. Stoichiometric and site characteristics of the binding of iron to human transferrin.
    J Biol Chem. 1978 Mar 25;253(6):1930-7 PMID: 204636
  97. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux.
    Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10812-7 PMID: 10485908
  98. A new role for the transferrin receptor in the release of iron from transferrin.
    Biochemistry. 1991 Jan 15;30(2):324-8 PMID: 1988034
  99. Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2.
    Blood. 2008 Nov 15;112(10):4268-75 PMID: 18776082
  100. The effects of an antibody to the rat transferrin receptor and of rat serum albumin on the uptake of diferric transferrin by rat hepatocytes.
    Biochim Biophys Acta. 1988 Sep 1;943(3):440-6 PMID: 3415986
  101. Interactions between isolated hepatocytes and Kupffer cells in iron metabolism: a possible role for ferritin as an iron carrier protein.
    Hepatology. 1988 Mar-Apr;8(2):296-301 PMID: 3356411
  102. The murine haemopexin receptor. Evidence that the haemopexin-binding site resides on a 20 kDa subunit and that receptor recycling is regulated by protein kinase C.
    Biochem J. 1991 Jun 1;276 ( Pt 2):417-25 PMID: 1646599
  103. Mechanisms of heme iron absorption: current questions and controversies.
    World J Gastroenterol. 2008 Jul 14;14(26):4101-10 PMID: 18636652
  104. The NRAMP family of metal-ion transporters.
    Biochim Biophys Acta. 2006 Jul;1763(7):609-20 PMID: 16908340
  105. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2.
    Mol Cell Biol. 2009 Feb;29(4):1007-16 PMID: 19075006
  106. The molecular mechanism of hepcidin-mediated ferroportin down-regulation.
    Mol Biol Cell. 2007 Jul;18(7):2569-78 PMID: 17475779
  107. Non-HFE haemochromatosis.
    World J Gastroenterol. 2007 Sep 21;13(35):4690-8 PMID: 17729390
  108. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.
    Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1148-53 PMID: 9448300
  109. Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence.
    Trends Microbiol. 2008 Jun;16(6):261-8 PMID: 18467097
  110. Iron homeostasis and erythropoiesis.
    Curr Top Dev Biol. 2008;82:141-67 PMID: 18282520
  111. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits.
    Nat Genet. 2001 Feb;27(2):181-6 PMID: 11175786
  112. Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3457-61 PMID: 3472216
  113. Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice.
    Development. 2004 Apr;131(8):1859-68 PMID: 15084469
  114. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation.
    J Clin Invest. 2002 Oct;110(7):1037-44 PMID: 12370282
  115. A mutation in Sec15l1 causes anemia in hemoglobin deficit (hbd) mice.
    Nat Genet. 2005 Nov;37(11):1270-3 PMID: 16227995
  116. Regulation of transferrin gene expression.
    FASEB J. 1992 Nov;6(14):3253-8 PMID: 1426763
  117. Intracellular copper transport in mammals.
    J Nutr. 2004 May;134(5):1003-6 PMID: 15113935
  118. The ceruloplasmin homolog hephaestin and the control of intestinal iron absorption.
    Blood Cells Mol Dis. 2002 Nov-Dec;29(3):367-75 PMID: 12547227
  119. Changes in the expression of intestinal iron transport and hepatic regulatory molecules explain the enhanced iron absorption associated with pregnancy in the rat.
    Gut. 2004 May;53(5):655-60 PMID: 15082582
  120. Sec15 is an effector for the Rab11 GTPase in mammalian cells.
    J Biol Chem. 2004 Oct 8;279(41):43027-34 PMID: 15292201
  121. Transferrin receptors and iron uptake during erythroid cell development.
    Biochim Biophys Acta. 1982 May 7;687(2):204-10 PMID: 6284220
  122. nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse.
    Blood. 2005 Nov 15;106(10):3625-31 PMID: 15994289
  123. Functional expression cloning and characterization of SFT, a stimulator of Fe transport.
    J Cell Biol. 1997 Nov 17;139(4):895-905 PMID: 9362508
  124. The orchestration of body iron intake: how and where do enterocytes receive their cues?
    Blood Cells Mol Dis. 2003 May-Jun;30(3):288-97 PMID: 12737947
  125. Identification of a human heme exporter that is essential for erythropoiesis.
    Cell. 2004 Sep 17;118(6):757-66 PMID: 15369674
  126. Role of ABCG2/BCRP in biology and medicine.
    Annu Rev Pharmacol Toxicol. 2006;46:381-410 PMID: 16402910
  127. Forging a field: the golden age of iron biology.
    Blood. 2008 Jul 15;112(2):219-30 PMID: 18606887
  128. Transferrin receptor 1 (TfR1) and putative stimulator of Fe transport (SFT) expression in iron deficiency and overload: an overview.
    Blood Cells Mol Dis. 2002 Nov-Dec;29(3):498-505 PMID: 12547240
  129. Iron and protein kinetics studied by means of doubly labeled human crystalline transferrin.
    J Clin Invest. 1961 Dec;40:2143-52 PMID: 14454385
  130. The regulation of cellular iron metabolism.
    Crit Rev Clin Lab Sci. 2007;44(5-6):413-59 PMID: 17943492
  131. Ultrastructural sequences during liver iron overload in genetic hemochromatosis.
    J Hepatol. 1997 Oct;27(4):628-38 PMID: 9365038
  132. Ferric citrate uptake by cultured rat hepatocytes is inhibited in the presence of transferrin.
    Eur J Biochem. 1998 Apr 1;253(1):139-45 PMID: 9578471
  133. Response to iron deprivation in Saccharomyces cerevisiae.
    Eukaryot Cell. 2008 Jan;7(1):20-7 PMID: 17993568
  134. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice.
    Blood. 2005 Oct 15;106(8):2879-83 PMID: 15961514
  135. The testicular iron shuttle: a "nurse" function of the Sertoli cells.
    J Androl. 1994 Sep-Oct;15(5):381-5 PMID: 7860417
  136. Pathogenesis of hereditary hemochromatosis.
    Clin Liver Dis. 2004 Nov;8(4):755-73, vii PMID: 15464654
  137. Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins.
    Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G931-9 PMID: 11557513
  138. Cellular regulation and molecular interactions of the ferritins.
    Cell Mol Life Sci. 2006 Mar;63(5):591-600 PMID: 16465450
  139. The macrophage scavenger receptor CD163.
    Immunobiology. 2005;210(2-4):153-60 PMID: 16164022
  140. The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis.
    Hum Mol Genet. 2006 Mar 15;15(6):953-64 PMID: 16467350
  141. Role of the hypoxia inducible factors HIF in iron metabolism.
    Cell Cycle. 2008 Jan 1;7(1):28-32 PMID: 18212530
  142. L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy.
    Nat Med. 2003 Sep;9(9):1187-94 PMID: 12937413
  143. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia.
    J Lab Clin Med. 1987 Dec;110(6):690-705 PMID: 3681112
  144. A cytosolic iron chaperone that delivers iron to ferritin.
    Science. 2008 May 30;320(5880):1207-10 PMID: 18511687
  145. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells.
    Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13612-7 PMID: 16950869
  146. Expression of the two mRNA isoforms of the iron transporter Nramp2/DMTI in mice and function of the iron responsive element.
    Biochem J. 2002 May 1;363(Pt 3):449-55 PMID: 11964145
  147. LRP: a multifunctional scavenger and signaling receptor.
    J Clin Invest. 2001 Sep;108(6):779-84 PMID: 11560943
  148. Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies.
    Am J Physiol Cell Physiol. 2004 Dec;287(6):C1769-75 PMID: 15317665
  149. Characterization of transferrin binding and specificity of the placental transferrin receptor.
    Arch Biochem Biophys. 1983 Aug;225(1):42-54 PMID: 6311110
  150. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22.
    Nat Genet. 2000 May;25(1):14-5 PMID: 10802645
  151. Regulation of plasma ferritin by the isolated perfused rat liver.
    Br J Haematol. 1981 Mar;47(3):403-12 PMID: 7459278
  152. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis.
    J Exp Med. 2005 Oct 3;202(7):955-65 PMID: 16203866
  153. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice.
    Nat Genet. 2001 Feb;27(2):209-14 PMID: 11175792
  154. Iron trafficking in the mitochondrion: novel pathways revealed by disease.
    Blood. 2005 Mar 1;105(5):1867-74 PMID: 15528311
  155. Iron Imports. II. Iron uptake at the apical membrane in the intestine.
    Am J Physiol Gastrointest Liver Physiol. 2005 Dec;289(6):G981-6 PMID: 16286504
  156. Iron-regulatory proteins: molecular biology and pathophysiological implications.
    Expert Rev Mol Med. 2007 Dec 05;9(33):1-13 PMID: 18053288
  157. Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis.
    Nat Rev Mol Cell Biol. 2005 Apr;6(4):345-51 PMID: 15803140
  158. Transferrin receptor is necessary for development of erythrocytes and the nervous system.
    Nat Genet. 1999 Apr;21(4):396-9 PMID: 10192390
  159. A heme export protein is required for red blood cell differentiation and iron homeostasis.
    Science. 2008 Feb 8;319(5864):825-8 PMID: 18258918
  160. Cloning and characterization of a mammalian proton-coupled metal-ion transporter.
    Nature. 1997 Jul 31;388(6641):482-8 PMID: 9242408
  161. Redox, transferrin-independent, and receptor-mediated endocytosis iron uptake systems in cultured human fibroblasts.
    J Biol Chem. 1993 Oct 15;268(29):21586-91 PMID: 8408010
  162. Iron metabolism meets signal transduction.
    Nat Genet. 2006 May;38(5):503-4 PMID: 16642010
  163. Nature of nontransferrin-bound iron.
    Eur J Clin Invest. 2002 Mar;32 Suppl 1:50-4 PMID: 11886432
  164. Copper and iron transport across the placenta: regulation and interactions.
    J Neuroendocrinol. 2008 Apr;20(4):427-31 PMID: 18266949
  165. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.
    Science. 2004 Dec 17;306(5704):2090-3 PMID: 15514116
  166. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption.
    Cell. 2006 Dec 1;127(5):917-28 PMID: 17129779
  167. Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron.
    J Biol Chem. 1994 Jun 10;269(23):16046-53 PMID: 8206903
  168. Regulation of transferrin function and expression: review and update.
    Biol Signals Recept. 1998 May-Jun;7(3):157-78 PMID: 9672759
  169. Structure of the human transferrin receptor-transferrin complex.
    Cell. 2004 Feb 20;116(4):565-76 PMID: 14980223
  170. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.
    Cell Metab. 2005 Mar;1(3):191-200 PMID: 16054062
  171. Direct interorganellar transfer of iron from endosome to mitochondrion.
    Blood. 2007 Jul 1;110(1):125-32 PMID: 17376890
  172. Identification of a hypoxia response element in the transferrin receptor gene.
    J Biol Chem. 1999 Aug 20;274(34):24147-52 PMID: 10446188
  173. Distinct targeting and recycling properties of two isoforms of the iron transporter DMT1 (NRAMP2, Slc11A2).
    Biochemistry. 2006 Feb 21;45(7):2294-301 PMID: 16475818
  174. Ferritin and ferritin isoforms I: Structure-function relationships, synthesis, degradation and secretion.
    Arch Physiol Biochem. 2007 Feb;113(1):30-54 PMID: 17522983
  175. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression.
    Cell Metab. 2005 Dec;2(6):399-409 PMID: 16330325
  176. Nramp 2 (DCT1/DMT1) expressed at the plasma membrane transports iron and other divalent cations into a calcein-accessible cytoplasmic pool.
    J Biol Chem. 2000 Nov 17;275(46):35738-45 PMID: 10942769
  177. The role of iron regulatory proteins in mammalian iron homeostasis and disease.
    Nat Chem Biol. 2006 Aug;2(8):406-14 PMID: 16850017
  178. Transferrin binding and iron uptake in mouse hepatocytes.
    Biochim Biophys Acta. 1983 Feb 16;762(1):102-10 PMID: 6830864
  179. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.
    Mol Cell. 2000 Feb;5(2):299-309 PMID: 10882071
  180. Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum.
    Cell Metab. 2008 Jan;7(1):79-85 PMID: 18177727
  181. Scara5 is a ferritin receptor mediating non-transferrin iron delivery.
    Dev Cell. 2009 Jan;16(1):35-46 PMID: 19154717
  182. The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity.
    Biochem J. 1994 Sep 15;302 ( Pt 3):875-9 PMID: 7945215
  183. Intracellular labile iron.
    Int J Biochem Cell Biol. 2008;40(3):350-4 PMID: 17451993
  184. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis.
    Ann N Y Acad Sci. 2004 Mar;1012:299-305 PMID: 15105274
  185. Effects of cell proliferation on the uptake of transferrin-bound iron by human hepatoma cells.
    Hepatology. 2003 Oct;38(4):967-77 PMID: 14512884
  186. Investigation of a role for reduction in ferric iron uptake by mouse duodenum.
    Biochim Biophys Acta. 1992 Jun 10;1135(2):141-6 PMID: 1616934
  187. Iron metabolism in the reticuloendothelial system.
    Crit Rev Biochem Mol Biol. 2003;38(1):61-88 PMID: 12641343
  188. The macrophage cell surface glyceraldehyde-3-phosphate dehydrogenase is a novel transferrin receptor.
    J Biol Chem. 2007 Feb 2;282(5):3252-61 PMID: 17121833
  189. Two genetic loci participate in the regulation by iron of the gene for the human transferrin receptor.
    Proc Natl Acad Sci U S A. 1988 Mar;85(6):1787-91 PMID: 3162307
  190. Labile iron pool: the main determinant of cellular response to oxidative stress.
    Mutat Res. 2003 Oct 29;531(1-2):81-92 PMID: 14637247
  191. Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation.
    Blood. 2000 Nov 1;96(9):3256-64 PMID: 11050011
  192. Identification of the receptor scavenging hemopexin-heme complexes.
    Blood. 2005 Oct 1;106(7):2572-9 PMID: 15947085
  193. Friedreich's ataxia: from disease mechanisms to therapeutic interventions.
    Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):438-43 PMID: 16677089
  194. Defective recovery and severe renal damage after acute hemolysis in hemopexin-deficient mice.
    Blood. 1999 Dec 1;94(11):3906-14 PMID: 10572107
  195. Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle.
    Proc Natl Acad Sci U S A. 2008 May 27;105(21):7410-5 PMID: 18495927
  196. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo.
    Science. 2004 Dec 17;306(5704):2087-90 PMID: 15604406
  197. Nramp1 equips macrophages for efficient iron recycling.
    Exp Hematol. 2008 Aug;36(8):929-37 PMID: 18456389
  198. Identification of the haemoglobin scavenger receptor.
    Nature. 2001 Jan 11;409(6817):198-201 PMID: 11196644
  199. Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport.
    Biochemistry. 1994 Oct 4;33(39):11850-7 PMID: 7918403
  200. Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum.
    Blood. 2002 Nov 15;100(10):3782-9 PMID: 12393650
  201. The anemia of "haemoglobin-deficit" (hbd/hbd) mice is caused by a defect in transferrin cycling.
    Exp Hematol. 2006 May;34(5):593-8 PMID: 16647565
Article Info
Journal
Cellular and molecular life sciences : CMLS
Abbr.
Cell Mol Life Sci
ISSN
1420-9071
DOI
10.1007/s00018-009-0051-1
Email
greg.anderson@qimr.edu.au
Published
2009-10-00
Epub
2009-00-31
Pages
3241-61
Language
English
Region
Switzerland
NLM ID
9705402
Subset
IM
External Links
PubMed source DOI: 10.1007/s00018-009-0051-1 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2