Hepcidin and ferroportin: The new players in iron metabolism

Seminars in Liver Disease

Volumn 31, Issue 3, 2011, Pages 272-279

  De Domenico, Ivana ^a   Ward, Diane McVey ^a   Kaplan, Jerry ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Ferroportin; genetics; hepcidin; iron

Indexed keywords

FERROPORTIN; HEPCIDIN;

ARTICLE; CELL MEMBRANE; DOWN REGULATION; ENZYME MECHANISM; HOMEOSTASIS; INTERNALIZATION; IRON METABOLISM; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN SYNTHESIS; TRANSCRIPTION REGULATION;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; CATION TRANSPORT PROTEINS; GENE EXPRESSION REGULATION; HUMANS; IRON;

EID: 80052689794     PISSN: 02728087     EISSN: 10988971     Source Type: Journal    
DOI: 10.1055/s-0031-1286058     Document Type: Article

References (63)

1. Nicolas G, Bennoun M, Devaux I et al. 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 98 15 8780-8785 (Pubitemid 32678104)
2. Nicolas G, Bennoun M, Porteu A et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci U S A 2002 99 7 4596-4601 (Pubitemid 34286030)
3. Roy CNMH, Mak H H., Akpan I, Losyev G, Zurakowski D, Andrews N C. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood 2007 109 9 4038-4044 (Pubitemid 46641759)
4. Weinstein D A., Roy C N., Fleming M D., Loda M F., Wolfsdorf J I., Andrews N C. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 2002 100 10 3776-3781 (Pubitemid 35303951)
5. Finberg K E., Heeney M M., Campagna D R. et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008 40 5 569-571 (Pubitemid 351601217)
6. Nemeth E, Tuttle M S., Powelson J et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004 306 5704 2090-2093 (Pubitemid 40007660)
7. Liu X B., Yang F, Haile D J. Functional consequences of ferroportin 1 mutations. Blood Cells Mol Dis 2005 35 1 33-46 (Pubitemid 40922773)
8. Donovan A, Brownlie A, Zhou Y et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 2000 403 6771 776-781 (Pubitemid 30111839)
9. McKie A T., Marciani P, Rolfs A et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 2000 5 2 299-309 (Pubitemid 30628088)
10. Troadec M B., Warner D, Wallace J et al. Targeted deletion of the mouse Mitoferrin1 gene: from anemia to protoporphyria. Blood 2011 117 20 5494-5502
11. Donovan A, Lima C A., Pinkus J L. et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 2005 1 3 191-200 (Pubitemid 43960600)
12. Montosi G, Donovan A, Totaro A et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 2001 108 4 619-623 (Pubitemid 32777742)
13. Pietrangelo A, Montosi G, Totaro A et al. Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. N Engl J Med 1999 341 10 725-732 (Pubitemid 29407372)
14. Mao J, McKean D M., Warrier S, Corbin J G., Niswander L, Zohn I E. The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure. Development 2010 137 18 3079-3088
15. Pietrangelo A. The ferroportin disease. Blood Cells Mol Dis 2004 32 1 131-138 (Pubitemid 38147710)
16. De Domenico I, Ward D M., Nemeth E et al. The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci U S A 2005 102 25 8955-8960 (Pubitemid 40881060)
17. Schimanski L M., Drakesmith H, Merryweather-Clarke A T. et al. In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood 2005 105 10 4096-4102 (Pubitemid 40656160)
18. Rice A E., Mendez M J., Hokanson C A., Rees D C., Björkman P J. Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J Mol Biol 2009 386 3 717-732
19. Wallace D F., Harris J M., Subramaniam V N. Functional analysis and theoretical modeling of ferroportin reveals clustering of mutations according to phenotype. Am J Physiol Cell Physiol 2010 298 1 C75-C84
20. McDonald C J., Wallace D F., Ostini L, Bell S J., Demediuk B, Subramaniam V N. G80S-linked ferroportin disease: classical ferroportin disease in an Asian family and reclassification of the mutant as iron transport defective. J Hepatol 2011 54 3 538-544
21. Drakesmith H, Schimanski L M., Ormerod E et al. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 2005 106 3 1092-1097 (Pubitemid 41076459)
22. Cunat S, Giansily-Blaizot M, Bismuth M et al, CHU Montpellier AOI 2004 Working Group. Global sequencing approach for characterizing the molecular background of hereditary iron disorders. Clin Chem 2007 53 12 2060-2069 (Pubitemid 350197288)
23. De Domenico I, Ward D M., Musci G, Kaplan J. Evidence for the multimeric structure of ferroportin. Blood 2007 109 5 2205-2209 (Pubitemid 46348224)
24. McGregor J A., Shayeghi M, Vulpe C D. et al. Impaired iron transport activity of ferroportin 1 in hereditary iron overload. J Membr Biol 2005 206 1 3-7 (Pubitemid 43163344)
25. Pignatti E, Mascheroni L, Sabelli M, Barelli S, Biffo S, Pietrangelo A. Ferroportin is a monomer in vivo in mice. Blood Cells Mol Dis 2006 36 1 26-32 (Pubitemid 43061484)
26. Schimanski L M., Drakesmith H, Talbott C et al. Ferroportin: lack of evidence for multimers. Blood Cells Mol Dis 2008 40 3 360-369 (Pubitemid 351508440)
27. Yeh K Y., Yeh M, Mims L, Glass J. Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium. Am J Physiol Gastrointest Liver Physiol 2009 296 1 G55-G65
28. Zohn I E., De Domenico I, Pollock A et al. The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease. Blood 2007 109 10 4174-4180 (Pubitemid 46743381)
29. De Domenico I, Vaughn M B., Yoon D, Kushner J P., Ward D M., Kaplan J. Zebrafish as a model for defining the functional impact of mammalian ferroportin mutations. Blood 2007 110 10 3780-3783 (Pubitemid 350159649)
30. De Domenico I, Lo E, Ward D M., Kaplan J. Human mutation D157G in ferroportin leads to hepcidin-independent binding of Jak2 and ferroportin down-regulation. Blood 2010 115 14 2956-2959
31. Chaston T, Chung B, Mascarenhas M et al. Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells. Gut 2008 57 3 374-382 (Pubitemid 351288105)
32. Paradkar P N., De Domenico I, Durchfort N, Zohn I, Kaplan J, Ward D M. Iron depletion limits intracellular bacterial growth in macrophages. Blood 2008 112 3 866-874
33. Ramey G, Deschemin J C., Durel B, Canonne-Hergaux F, Nicolas G, Vaulont S. Hepcidin targets ferroportin for degradation in hepatocytes. Haematologica 2010 95 3 501-504
34. Nemeth E, Preza G C., Jung C L., Kaplan J, Waring A J., Ganz T. The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 2006 107 1 328-333 (Pubitemid 43053559)
35. De Domenico I, Nemeth E, Nelson J M. et al. The hepcidin-binding site on ferroportin is evolutionarily conserved. Cell Metab 2008 8 2 146-156
36. Fernandes A, Preza G C., Phung Y et al. The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood 2009 114 2 437-443
37. De Domenico I, Lo E, Ward D M., Kaplan J. Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2. Proc Natl Acad Sci U S A 2009 106 10 3800-3805
38. De Domenico I, Ward D M., Langelier C et al. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 2007 18 7 2569-2578 (Pubitemid 47025722)
39. Osaki S, Johnson D A., Frieden E. The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. J Biol Chem 1966 241 12 2746-2751
40. Dowdy R P., Matrone G. A copper-molybdenum complex: its effects and movement in the piglet and sheep. J Nutr 1968 95 2 197-201
41. Lee G R., Nacht S, Lukens J N., Cartwright G E. Iron metabolism in copper-deficient swine. J Clin Invest 1968 47 9 2058-2069
42. Patel B N., David S. A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes. J Biol Chem 1997 272 32 20185-20190 (Pubitemid 27340128)
43. Osaki S, Johnson D A., Frieden E. The mobilization of iron from the perfused mammalian liver by a serum copper enzyme, ferroxidase I. J Biol Chem 1971 246 9 3018-3023
44. Sarkar J SV, Seshadri V, Tripoulas N A., Ketterer M E., Fox P L. Role of ceruloplasmin in macrophage iron efflux during hypoxia. J Biol Chem 2003 278 45 44018-44024 (Pubitemid 37377141)
45. Lahey M E., Gubler C J., Chase M S., Cartwright G E., Wintrobe M M. Studies on copper metabolism. II. Hematologic manifestations of copper deficiency in swine. Blood 1952 7 11 1053-1074
46. Harris E D. The iron-copper connection: the link to ceruloplasmin grows stronger. Nutr Rev 1995 53 6 170-173
47. Vulpe C D., Kuo Y M., Murphy T L. et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999 21 2 195-199 (Pubitemid 29070366)
48. Harris Z L., Klomp L W., Gitlin J D. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am J Clin Nutr 1998 67 5, Suppl 972S-977S (Pubitemid 28198819)
49. Bernstein S E. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J Lab Clin Med 1987 110 6 690-705 (Pubitemid 18033263)
50. Hamill R L., Woods J C., Cook B A. Congenital atransferrinemia. A case report and review of the literature. Am J Clin Pathol 1991 96 2 215-218
51. De Domenico I, Ward D M., di Patti M C. et al. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J 2007 26 12 2823-2831 (Pubitemid 46975784)
52. Delaby C, Pilard N, Puy H, Canonne-Hergaux F. Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by haem, followed by iron-dependent protein expression. Biochem J 2008 411 1 123-131 (Pubitemid 351482354)
53. Marro S, Chiabrando D, Messana E et al. Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position -7007 of the FPN1 promoter. Haematologica 2010 95 8 1261-1268
54. Park B Y., Chung J. Effects of various metal ions on the gene expression of iron exporter ferroportin-1 in J774 macrophages. Nurs Res Pract 2008 2 4 317-321
55. Zoller H, Theurl I, Koch R, Kaser A, Weiss G. Mechanisms of iron mediated regulation of the duodenal iron transporters divalent metal transporter 1 and ferroportin 1. Blood Cells Mol Dis 2002 29 3 488-497
56. Jacolot S, Férec C, Mura C. Iron responses in hepatic, intestinal and macrophage/monocyte cell lines under different culture conditions. Blood Cells Mol Dis 2008 41 1 100-108
57. Knutson M D., Vafa M R., Haile D J., Wessling-Resnick M. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood 2003 102 12 4191-4197 (Pubitemid 37487007)
58. Troadec M B., Ward D M., Lo E, Kaplan J, De Domenico I. Induction of FPN1 transcription by MTF-1 reveals a role for ferroportin in transition metal efflux. Blood 2010 116 22 4657-4664
59. Harada N, Kanayama M, Maruyama A et al. Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages. Arch Biochem Biophys 2011 508 1 101-109
60. Abboud S, Haile D J. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 2000 275 26 19906-19912 (Pubitemid 30441595)
61. Muckenthaler M U., Galy B, Hentze M W. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr 2008 28 197-213
62. Mok H, Mendoza M, Prchal J T., Balogh P, Schumacher A. Dysregulation of ferroportin 1 interferes with spleen organogenesis in polycythaemia mice. Development 2004 131 19 4871-4881 (Pubitemid 39433472)
63. Zhang D L., Hughes R M., Ollivierre-Wilson H, Ghosh M C., Rouault T A. A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression. Cell Metab 2009 9 5 461-473