Iron homeostasis

Annual Review of Physiology

Volumn 69, Issue , 2007, Pages 69-85

  Andrews, Nancy C ^a   Schmidt, Paul J ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

Anemia; Hemochromatosis; Transferrin; Transport

Indexed keywords

CERULOPLASMIN; HEMOGLOBIN; IRON; IRON REGULATORY FACTOR; MESSENGER RNA; MYOGLOBIN; OXYGEN RADICAL; TRANSFERRIN RECEPTOR;

ANEMIA; HEMOCHROMATOSIS; HOMEOSTASIS; HUMAN; IRON ABSORPTION; IRON BALANCE; IRON TRANSPORT; MAMMAL CELL; MEMBRANE CONDUCTANCE; MOLECULAR MECHANICS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN TRANSPORT; REGULATORY MECHANISM; REVIEW;

ANIMALS; BIOLOGICAL TRANSPORT, ACTIVE; HOMEOSTASIS; HUMANS; INTESTINAL ABSORPTION; IRON;

EID: 33947431648     PISSN: 00664278     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.physiol.69.031905.164337     Document Type: Review

References (115)

1. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, et al. 2001. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291:1755-59
2. Gunshin H, Starr CN, Direnzo C, Fleming MD, Jin J, et al. 2005. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood 106(8):2879-83.
3. Ohgami RS, Campagna DR, McDonald A, Fleming MD. 2006. The Steap proteins are metalloreductases. Blood 108:1388-94
4. Fleming MD, Trenor CC, Su MA, Foernzler D, Beier DR, et al. 1997. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat. Genet. 16:383-86
5. Gunshin H, Fujiwara Y, Custodio AO, Direnzo C, Robine S, Andrews NC. 2005. Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J. Clin. Invest. 115:1258-66
6. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, et al. 1997. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482-88
7. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. 1998. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc. Natl. Acad. Sci. USA 95:1148-53
8. Xu H, Jin J, DeFelice LJ, Andrews NC, Clapham DE. 2004. A spontaneous, recurrent mutation in divalent metal transporter-1 exposes a calcium entry pathway. PLoS Biol. 2:E50
9. Beaumont C, Delaunay J, Hetet G, Grandchamp B, de Montalembert M, Tchernia G. 2006. Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood 107:4168-70
10. Iolascon A, d'Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C. 2006. Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood 107:349-54
11. Mims MP, Guan Y, Pospisilova D, Priwitzerova M, Indrak K, et al. 2005. Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood 105:1337-42
12. Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, et al. 2005. Identification of an intestinal heme transporter. Cell 122:789-801
13. Abboud S, Haile DJ. 2000. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275:19906-12
14. Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, et al. 2000. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403:776-81
15. McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, et al. 2000. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol. Cell 5:299-309
16. Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, et al. 2005. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 1:191-200
17. Harris ZL, Durley AP, Man TK, Gitlin JD. 1999. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc. Natl. Acad. Sci. USA 96:10812-17
18. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, et al. 1999. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat. Genet. 21:195-99
19. Cherukuri S, Potla R, Sarkar J, Nurko S, Harris ZL, Fox PL. 2005. Unexpected role of ceruloplasmin in intestinal iron absorption. Cell Metab. 2:309-19
20. Uchida T, Akitsuki T, Kimura H, Tanaka T, Matsuda S, Kariyone S. 1983. Relationship among plasma iron, plasma iron turnover, and reticuloendothelial iron release. Blood 61:799-802
21. Hentze MW, Muckenthaler MU, Andrews NC. 2004. Balancing acts: molecular control of mammalian iron metabolism. Cell 117:285-97
22. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. 1999. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat. Genet. 21:396-99
23. Ned RM, Swat W, Andrews NC. 2003. Transferrin receptor 1 is differentially required in lymphocyte development. Blood 102:3711-18
24. Larrick J, Flyman E. 1984. Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor. N. Engl. J. Med. 311:214-18
25. Bernstein SE. 1987. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J. Lab. Clin. Med. 110:690-705
26. Trenor CC, Campagna DR, Sellers VM, Andrews NC, Fleming MD. 2000. The molecular defect in hypotransferrinemic mice. Blood 96:1113-18
27. Asada-Senju M, Maeda T, Sakata T, Hayashi A, Suzuki T. 2002. Molecular analysis of the transferrin gene in a patient with hereditary hypotransferrinemia. J. Hum. Genet. 47:355-59
28. Beutler E, Gelbart T, Lee P, Trevino R, Fernandez MA, Fairbanks VF. 2000. Molecular characterization of a case of atransferrinemia. Blood 96:4071-74
29. Dickinson T, Connor JR. 1994. Histological analysis of selected brain regions of hypotransferrinemic mice. Brain Res. 635:169-78
30. Craven CM, Alexander J, Eldridge M, Kushner JP, Bernstein S, Kaplan J. 1987. Tissue distribution and clearance kinetics of nontransferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis. Proc. Natl. Acad. Sci. USA 84:3457-61
31. Finch C. 1994. Regulators of iron balance in humans. Blood 84:1697-702
32. Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, et al. 2005. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat. Genet. 37:1264-69
33. Ponka P. 1997. Tissue-specific regulation of iron metabolism and heme synthesis: distinct control mechanisms in erythroid cells. Blood 89:1-25
34. Shaw GC, Cope JJ, Li L, Corson K, Hersey C, et al. 2006. Mitoferrin is essential for erythroid iron assimilation. Nature 440:96-100
35. Quigley JG, Yang Z, Worthington MT, Phillips JD, Sabo KM, et al. 2004. Identification of a human heme exporter that is essential for erythropoiesis. Cell 118:757-66
36. Neckers LM, Cossman J. 1983. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleuidn 2. Proc. Natl. Acad. Sci. USA 80:3494-98
37. Neckers LM, Yenokida G, James SP. 1984. The role of the transferrin receptor in human B lymphocyte activation. J. Immunol. 133:2437-41
38. Batista A, Millan J, Mittelbrunn M, Sanchez-Madrid F, Alonso MA. 2004. Recruitment of transferrin receptor to immunological synapse in response to TCR engagement. J. Immunol. 172:6709-14
39. Salmeron A, Borroto A, Fresno M, Crumpton MJ, Ley SC, Alarcon B. 1995. Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR zeta-chain. J. Immunol. 154:1675-83
40. Woodward JE, Bayer AL, Chavin KD, Boleza KA, Baliga P. 1998. Anti-transferrin receptor monoclonal antibody: a novel immunosuppressant. Transplantation 65:6-9
41. Yang J, Goetz D, Li JY, Wang W, Mori K, et al. 2002. An iron delivery pathway mediated by a lipocalin. Mol. Cell 10:1045-56
42. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. 2002. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell 10:1033-43
43. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, et al. 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432:917-21
44. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. 2004. Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci. 5:863-73
45. Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, et al. 2003. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 37:899-909
46. Kielmanowicz MG, Laham N, Coligan JE, Lemonnier F, Ehrlich R. 2005. Mouse HFE inhibits Tf-uptake and iron accumulation but induces nontransferrin bound iron (NTBI)-uptake in transformed mouse fibroblasts. J. Cell Physiol. 202:105-14
47. Mwanjewe J, Grover AK. 2004. Role of transient receptor potential canonical 6 (TRPC6) in nontransferrin-bound iron uptake in neuronal phenotype PC12 cells. Biochem. J. 378:975-82
48. 2+ dependence of nontransferrin-bound iron uptake in PC12 cells. J. Biol. Chem. 275:33512-15
49. Barisani D, Berg CL, Wessling-Resnick M, Gollan JL. 1995. Evidence for a low Km transporter for nontransferrin-bound iron in isolated rat hepatocytes. Am. J. Physiol. 269:G570-76
50. Randell EW, Parkes JG, Olivieri NF, Templeton DM. 1994. Uptake of nontransferrin bound iron by both reductive and nonreductive processes is modulated by intracellular iron. J. Biolog. Chem. 269:16046-53
51. Inman RS, Coughlan MM, Wessling-Resnick M. 1994. Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport. Biochemistry 33:11850-57
52. Worthington MT, Browne L, Battle EH, Luo RQ. 2000. Functional properties of transfected human DMT1 iron transporter. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G1265-73
53. Lam-Yuk-Tseung S, Govoni G, Forbes J, Gros P. 2003. Iron transport by Nramp2/DMT1: pH regulation of transport by 2 histidines in transmembrane domain 6. Blood 101:3699-707
54. 2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nat. Med. 9:1187-94
55. Theil EC. 2003. Ferritin: at the crossroads of iron and oxygen metabolism. J. Nutr. 133:S1549-53
56. Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, et al. 2001. A human mitochondrial ferritin encoded by an intronless gene. J. Biol. Chem. 276:24437-40
57. Cazzola M, Invernizzi R, Bergamaschi G, Levi S, Corsi B, et al. 2003. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood 101:1996-2000
58. Rouault TA, Stout CD, Kaptain S, Harford JB, Klausner RD. 1991. Structural relationship between an iron-regulated RNA-binding protein (IRE-BP) and aconitase: functional implications. Cell 64:881-83
59. Kaptain S, Downey WE, Tang C, Philpott C, Haile D, et al. 1991. A regulated RNA binding protein also possesses aconitase activity. Proc. Natl. Acad. Sci. USA 88:10109-13
60. Iwai K, Drake SK, Wehr NB, Weissman AM, LaVaute T, et al. 1998. Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins. Proc. Natl. Acad. Sci. USA 95:4924-28
61. Pantopoulos K. 2004. Iron metabolism and the IRE/IRP regulatory system: an update. Ann. N.Y. Acad. Sci. 1012:1-13
62. Meyron-Holtz EG, Ghosh MC, Iwai K, LaVaute T, Brazzolotto X, et al. 2004. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J. 23:386-95
63. LaVaute T, Smith S, Cooperman S, Iwai K, Land W, et al. 2001. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet. 27:209-14
64. 63a. Galy B, Holter SM, Klopstock T, Ferring D, Becker L, et al. 2006. Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symtpmatic neurodegeneration in the mouse. Nat. Genet. 38:967-69
65. Meyron-Holtz EG, Ghosh MC, Rouault TA. 2004. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306:2087-90
66. Beaumont C, Leneuve P, Devaux I, Scoazec JY, Berthier M, et al. 1995. Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinemia and cataract. Nat. Genet. 11:444-46
67. Kato J, Fujikawa K, Kanda M, Fukuda N, Sasaki K, et al. 2001. A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am J. Hum. Genet. 69:191-97
68. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, et al. 2001. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc. Natl. Acad. Sci. USA 98:8780-85
69. Park CH, Valore EV, Waring AJ, Ganz T. 2001. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem. 276:7806-10
70. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, et al. 2001. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J. Biol. Chem. 276:7811-19
71. Hunter HN, Fulton DB, Ganz T, Vogel HJ. 2002. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. J. Biol. Chem. 277:37597-603
72. Melino S, Garlando L, Patamia M, Paci M, Petruzzelli R. 2005. A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25. J. Pept. Res. 66:65-71
73. Ilyin G, Courselaud B, Troadec MB, Pigeon C, Alizadeh M, et al. 2003. Comparative analysis of mouse hepcidin 1 and 2 genes: evidence for different patterns of expression and coinducibility during iron overload. FEBS Lett. 542:22-26
74. Peyssonnaux C, Zinkernagel AS, Datta V, Lauth X, Johnson RS, Nizet V. 2006. TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 107:3727-32
75. Lou DQ, Nicolas G, Lesbordes JC, Viatte L, Grimber G, et al. 2004. Functional differences between hepcidin 1 and 2 in transgenic mice. Blood 103:2816-21
76. Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, et al. 2002. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. USA 99:4596-601
77. Viatte L, Lesbordes-Brion JC, Lou DQ, Bennoun M, Nicolas G, et al. 2005. Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice. Blood 105:4861-64
78. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, et al. 2002. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 110:1037-44
79. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. 2002. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776-81
80. Nemeth E, Turtle MS, Powelson J, Vaughn MB, Donovan A, et al. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090-93
81. Courselaud B, Pigeon C, Inoue Y, Inoue J, Gonzalez FJ, et al. 2002. C/EBPα regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism. J. Biol. Chem. 277:41163-70
82. Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, et al. 2006. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat. Genet. 38:531-39
83. Wang RH, Li C, Xu X, Zheng Y, Xiao C, et al. 2005. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab. 2:399-409
84. Niederkofler V, Salie R, Sigrist M, Arber S. 2004. Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J. Neurosci. 24:808-18
85. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, et al. 2004. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 113:1271-76
86. Wrighting DM, Andrews NC. 2006. Interleukin-6 induces hepcidin expression through STAT3. Blood. In press
87. Donovan A, Brownlie A, Dorschner MO, Zhou Y, Pratt SJ, et al. 2002. The zebrafish mutant gene chardonnay (cdy) encodes divalent metal transporter 1 (DMT1). Blood 100:4655-59
88. Andrews NC. 2000. Iron homeostasis: insights from genetics and animal models. Nat. Rev. Genet. 1:208-17
89. Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, et al. 2000. The gene TFR2 is mutated in a new type of hemochromatosis mapping to 7q22. Nat. Genet. 25:14-15
90. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, et al. 1996. A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis. Nat. Genet. 13:399-408
91. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, et al. 2004. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat. Genet. 36:77-82
92. Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, et al. 2003. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat. Genet. 33:21-22
93. Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, et al. 2001. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J. Clin. Invest. 108:619-23
94. Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, et al. 2001. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat. Genet. 28:213-14
95. De Domenico I, Ward DM, Musci G, Kaplan J. 2006. Iron overload due to mutations in ferroportin. Haematologica 91:92-95
96. Drakesmith H, Schimanski LM, Ormerod E, Merryweather-Clarke AT, Viprakasit V, et al. 2005. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 106:1092-97
97. De Domenico I, Ward DM, Nemeth E, Vaughn MB, Musci G, et al. 2005. The molecular basis of ferroportin-linked hemochromatosis. Proc. Natl. Acad. Sci. USA 102:8955-60
98. Fillet G, Beguin Y, Baldelli L. 1989. Model of reticuloendothelial iron metabolism in humans: abnormal behavior in idiopathic hemochromatosis and in inflammation. Blood 74:844-51
99. Ajioka RS, Kushner JP. 2003. Clinical consequences of iron overload in hemochromatosis homozygotes. Blood 101:3351-53; discussion 4-8
100. Ajioka RS, Kushner JP. 2003. Rebuttal to Beutler. Blood 101:3358
101. Beutler E. 2003. Penetrance of hemochromatosis. Gut 52:610-11
102. Beutler E. 2003. Rebuttal to Ajioka and Kushner. Blood 101:3354-57
103. Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, et al. 2003. Disrupted hepcidin regulation in HFE-associated hemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361:669-73
104. Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C. 2005. Hepcidin is decreased in TFR2 hemochromatosis. Blood 105:1803-6
105. Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, et al. 1998. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93:111-23
106. Ajioka RS, Jorde LB, Gruen JR, Dimitrova D, Barrow J, et al. 1997. Haplotype analysis of hemochromatosis: evaluation of different linkage-disequilibrium approaches and evolution of disease chromosomes. Am J. Hum. Genet. 60:1439-47
107. Levy JE, Montross LK, Cohen DE, Fleming MD, Andrews NC. 1999. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 94:9-11
108. Roy CN, Enns CA. 2000. Iron homeostasis: new tales from the crypt. Blood 96:4020-27
109. Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S, et al. 1999. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J. Biol. Chem. 274:20826-32
110. Robb A, Wessling-Resnick M. 2004. Regulation of transferrin receptor 2 protein levels by transferrin. Blood 104:4294-99
111. Johnson MB, Enns CA. 2004. Regulation of transferrin receptor 2 by transferrin: Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104:4287-93
112. Kearney SL, Nemeth E, Neufeld EJ, Thapa D, Ganz T, et al. 2005. Urinary hepcidin in congenital chronic anemias. Pediatr. Blood Cancer
113. Papanikolaou G, Tzilianos M, Christakis JI, Bogdanos D, Tsimirika K, et al. 2005. Hepcidin in iron overload disorders. Blood 105:4103-5
114. Harris ZL, Klomp LW, Gitlin JD. 1998. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am. J. Clin. Nutr. 67:S972-77
115. Donavan A, Roy CN, Andrews NC. 2006. The ins and outs of iron homeostasis. Physiology 21:115-23