Mammalian iron transport
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Crosa JH, Mey AR, Payne SM (eds) (2004) Iron transport in bacteria. American Society for Microbiology, Washington, DC
Philpott CC, Protchenko O (2008) Response to iron deprivation in Saccharomyces cerevisiae. Eukaryot Cell 7:20–27
Sutak R, Lesuisse E, Tachezy J, Richardson DR (2008) Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence. Trends Microbiol 16:261–268
Rouault TA, Tong WH (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6:345–351
Lill R, Mühlenhoff U (2006) Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms. Annu Rev Cell Dev Biol 22:457–486
Crichton R (2001) Inorganic biochemistry of iron metabolism. From Molecular mechanisms to clinical consequences. 2nd edn. Wiley, New York
Castagnetto JM, Hennessy SW, Roberts VA, Getzoff ED, Tainer JA, Pique ME (2002) MDB: the Metalloprotein Database and Browser at The Scripps Research Institute. Nucl Acids Res 30:379–382. http://metallo.scripps.edu
Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275:161–203
Koorts AM, Viljoen M (2007) Ferritin and ferritin isoforms I: structure-function relationships, synthesis, degradation and secretion. Arch Physiol Biochem 113:30–54
Iancu TC, Deugnier Y, Halliday JW, Powell LW, Brissot P (1997) Ultrastructural sequences during liver iron overload in genetic hemochromatosis. J Hepatol 27:628–638
Trinder D, Morgan E (2001) Uptake of transferrin-bound iron by mammalian cells. In: Templeton DM (ed) Molecular and cellular iron transport. Marcel Dekker, New York, pp 427–449
Chua AC, Graham RM, Trinder D, Olynyk JK (2007) The regulation of cellular iron metabolism. Crit Rev Clin Lab Sci 44:413–459
Parkes JG, Templeton DM (2001) Transport of non-transferrin-bound iron by hepatocytes. In: Templeton DM (ed) Molecular and cellular iron transport. Marcel Dekker, New York, pp 451–466
Enns CA (2001) The transferrin receptor. In: Templeton DM (ed) Molecular and cellular iron transport. Marcel Dekker, New York, pp 71–94
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 21:396–399
Lawrence CM, Ray S, Babyonyshev M, Galluser R, Borhani DW, Harrison SC (1999) Crystal structure of the ectodomain of human transferrin receptor. Science 286:779–782
Cheng Y, Zak O, Aisen P, Harrison SC, Walz T (2004) Structure of the human transferrin receptor-transferrin complex. Cell 116:565–576
Tsunoo H, Sussman HH (1983) Characterization of transferrin binding and specificity of the placental transferrin receptor. Arch Biochem Biophys 225:42–54
Klausner RD, Ashwell G, van Renswoude J, Harford JB, Bridges KR (1983) Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. Proc Natl Acad Sci USA 80:2263–2266
Watkins JA, Altazan JD, Elder P, Li C-Y, Nunez M-T, Cui X-X, Glass J (1992) Kinetic characterization of reductant dependent processes in iron mobilization from endocytic vesicles. Biochemistry 31:5820–5830
Bali PK, Zak O, Aisen P (1991) A new role for the transferrin receptor in the release of iron from transferrin. Biochemistry 30:324–328
Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE, Fleming MD (2005) Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet 37:1264–1269
Ohgami RS, Campagna DR, Antiochos B, Wood EB, Sharp JJ, Barker JE, Fleming MD (2005) nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse. Blood 106:3625–3631
Ohgami RS, Campagna DR, McDonald A, Fleming MD (2006) The Steap proteins are metalloreductases. Blood 108:1388–1394
Sendamarai AK, Ohgami RS, Fleming MD, Lawrence CM (2008) Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle. Proc Natl Acad Sci USA 105:7410–7415
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 95:1148–1153
Katz JH (1961) Iron and protein kinetics studied by means of doubly labeled human crystalline transferrin. J Clin Invest 40:2143–2152
Lim JE, Jin O, Bennett C, Morgan K, Wang F, Trenor CC 3rd, Fleming MD, Andrews NC (2005) A mutation in Sec15l1 causes anemia in hemoglobin deficit (hbd) mice. Nat Genet 37:1270–1273
White RA, Boydston LA, Brookshier TR, McNulty SG, Nsumu NN, Brewer BP, Blackmore K (2005) Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking. Genomics 86:668–673
Garrick LM, Edwards JA, Hoke JE, Bannerman RM (1987) Diminished acquisition of iron by reticulocytes from mice with hemoglobin deficit. Exp Hematol 15:671–675
Zhang AS, Sheftel AD, Ponka P (2006) The anemia of “haemoglobin-deficit” (hbd/hbd) mice is caused by a defect in transferrin cycling. Exp Hematol 34:593–598
Zhang XM, Ellis S, Sriratana A, Mitchell CA, Rowe T (2004) Sec15 is an effector for the Rab11 GTPase in mammalian cells. J Biol Chem 279:43027–43034
Anderson GJ, Powell LW, Halliday JW (1994) The endocytosis of transferrin by rat intestinal epithelial cells. Gastroenterology 106:414–422
Trinder D, Zak O, Aisen P (1996) Transferrin receptor-independent uptake of differic transferrin by human hepatoma cells with antisense inhibition of receptor expression. Hepatology 23:1512–1520
Trinder D, Morgan EH, Baker E (1988) 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 943:440–446
Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S, Gombart AF, Koeffler HP (1999) Molecular cloning of transferrin receptor 2: a new member of the transferrin receptor-like family. J Biol Chem 274:20826–20832
Lee AW, Oates PS, Trinder D (2003) Effects of cell proliferation on the uptake of transferrin-bound iron by human hepatoma cells. Hepatology 38:967–977
Robb AD, Ericsson M, Wessling-Resnick M (2004) Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies. Am J Physiol 287:C1769–C1775
Morgan EH, Smith GD, Peters TJ (1986) Uptake and subcellular processing of 59Fe-125I-labelled transferrin by rat liver. Biochem J 237:163–173
Trinder D, Morgan EH, Baker E (1986) The mechanisms of iron uptake by fetal rat hepatocytes in culture. Hepatology 6:852–858
Fleming RE, Migas MC, Holden CC, Waheed A, Britton RS, Tomatsu S, Bacon BR, Sly WS (2000) Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proc Natl Acad Sci USA 97:2214–2219
Deaglio S, Capobianco A, Cali A, Bellora F, Alberti F, Righi L, Sapino A, Camaschella C, Malavasi F (2002) Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and polyclonal antiserum. Blood 100:3782–3789
Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P (2000) The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 25:14–15
Fleming RE, Ahmann JR, Migas MC, Waheed A, Koeffler HP, Kawabata H, Britton RS, Bacon BR, Sly WS (2002) Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci USA 99:10653–10658
Raje CI, Kumar S, Harle A, Nanda JS, Raje M (2007) The macrophage cell surface glyceraldehyde-3-phosphate dehydrogenase is a novel transferrin receptor. J Biol Chem 282:3252–3261
Thorstensen K, Romslo I (1990) The role of transferrin in the mechanism of cellular iron uptake. Biochem J 271:1–10
Oshiro S, Nakajima H, Markello T, Krasnewich D, Bernardini I, Gahl WA (1993) Redox, transferrin-independent, and receptor-mediated endocytosis iron uptake systems in cultured human fibroblasts. J Biol Chem 268:21586–21591
Cole ES, Glass J (1983) Transferrin binding and iron uptake in mouse hepatocytes. Biochim Biophys Acta 762:102–110
Thorstensen K, Romslo I (1988) Uptake of iron from transferrin by isolated rat hepatocytes. A redox-mediated plasma membrane process? J Biol Chem 263:8844–8850
Trinder D, Morgan E (1997) Inhibition of uptake of transferrin-bound iron by human hepatoma cells by nontransferrin-bound iron. Hepatology 26:691–698
Graham RM, Morgan EH, Baker E (1998) Ferric citrate uptake by cultured rat hepatocytes is inhibited in the presence of transferrin. Eur J Biochem 253:139–145
Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488
Courville P, Chaloupka R, Cellier MF (2006) Recent progress in structure-function analyses of Nramp proton-dependent metal-ion transporters. Biochem Cell Biol 84:960–978
Fleming MD, Trenor CC 3rd, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC (1997) Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16:383–386
Nevo Y (2008) Site-directed mutagenesis investigation of coupling properties of metal ion transport by DCT1. Biochim Biophys Acta 1778:334–341
Li H, Gu JD, Sun H (2008) 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 102:1257–1266
Bowen BJ, Morgan EH (1987) Anemia of the Belgrade rat: evidence for defective membrane transport of iron. Blood 70:38–44
Mackenzie B, Garrick MD (2005) Iron imports. II. Iron uptake at the apical membrane in the intestine. Am J Physiol 289:G981–G986
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 115:1258–1266
Picard V, Govoni G, Jabado N, Gros P (2000) Nramp 2 (DCT1/DMT1) expressed at the plasma membrane transports iron and other divalent cations into a calcein-accessible cytoplasmic pool. J Biol Chem 275:35738–35745
Nevo Y, Nelson N (2006) The NRAMP family of metal-ion transporters. Biochim Biophys Acta 1763:609–620
Vidal SM, Malo D, Vogan K, Skamene E, Gros P (1993) Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73:469–485
Gruenheid S, Pinner E, Desjardins M, Gros P (1997) Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med 185:717–730
Goswami T, Bhattacharjee A, Babal P, Searle S, Moore E, Li M, Blackwell JM (2001) Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation antiporter. Biochem J 354:511–519
Wyllie S, Seu P, Goss JA (2002) The natural resistance-associated macrophage protein 1 Slc11a1 (formerly Nramp1) and iron metabolism in macrophages. Microbes Infect 4:351–359
Soe-Lin S, Sheftel AD, Wasyluk B, Ponka P (2008) Nramp1 equips macrophages for efficient iron recycling. Exp Hematol 36:929–937
Bernstein SE (1987) Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J Lab Clin Med 110:690–705
Hayashi A, Wada Y, Suzuki T, Shimizu A (1993) Studies on familial hypotransferrinemia: unique clinical course and molecular pathology. Am J Hum Genet 53:201–213
Aisen P, Leibman A, Zweier J (1978) Stoichiometric and site characteristics of the binding of iron to human transferrin. J Biol Chem 253:1930–1937
Breuer W, Shvartsman M, Cabantchik ZI (2008) Intracellular labile iron. Int J Biochem Cell Biol 40:350–354
Craven CM, Alexander J, Eldridge M, Kushner JP, Bernstein S, Kaplan J (1987) Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis. Proc Natl Acad Sci USA 84:3457–3461
Wright TL, Brissot P, Ma W-L, Weisinger RA (1986) Characterization of non-transferrin-bound iron clearance by rat liver. J Biol Chem 261:10909–10914
Gutierrez JA, Yu J, Rivera S, Wessling-Resnick M (1997) Functional expression cloning and characterization of SFT, a stimulator of Fe transport. J Cell Biol 139:895–905 [Correction in (1999) J Cell Biol 147, following p 204]
Barisani D, Conte D (2002) Transferrin receptor 1 (TfR1) and putative stimulator of Fe transport (SFT) expression in iron deficiency and overload: an overview. Blood Cells Mol Dis 29:498–505
Gehrke SG, Riedel HD, Herrmann T, Hadaschik B, Bents K, Veltkamp C, Stremmel W (2003) 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 101:3288–3293
Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA 103:13612–13617
Oudit GY, Sun H, Trivieri MG, Koch SE, Dawood F, Ackerley C, Yazdanpanah M, Wilson GJ, Schwartz A, Liu PP, Backx PH (2003) L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nat Med 9:1187–1194
Randell EW, Parkes JG, Olivieri NF, Templeton DM (1994) Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. J Biol Chem 269:16046–16053
Lim SK, Kim H, Lim SK, bin Ali A, Lim YK, Wang Y, Chong SM, Costantini F, Baumman H (1998) Increased susceptibility in Hp knockout mice during acute hemolysis. Blood 92:1870–1877
Tolosano E, Hirsch E, Patrucco E, Camaschella C, Navone R, Silengo L, Altruda F (1999) Defective recovery and severe renal damage after acute hemolysis in hemopexin-deficient mice. Blood 94:3906–3914
Wassell J (2000) Haptoglobin: function and polymorphism. Clin Lab 46:547–552
Moestrup SK, Moller HJ (2004) CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. Ann Med 36:347–354
Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409:198–201
Fabriek BO, Dijkstra CD, van den Berg TK (2005) The macrophage scavenger receptor CD163. Immunobiol 210:153–160
Tolosano E, Altruda F (2002) Hemopexin: structure, function, and regulation. DNA Cell Biol 21:297–306
Herz J, Strickland DK (2001) LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 108:779–784
Hvidberg V, Maniecki MB, Jacobsen C, Hojrup P, Moller HJ, Moestrup SK (2005) Identification of the receptor scavenging hemopexin-heme complexes. Blood 106:2572–2579
Smith A, Farooqui SM, Morgan WT (1991) 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 276:417–425
Latunde-Dada GO, Simpson RJ, McKie AT (2006) Recent advances in mammalian haem transport. Trends Biochem Sci 31:182–188
Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, Khan Y, Warley A, McCann FE, Hider RC, Frazer DM, Anderson GJ, Vulpe CD, Simpson RJ, McKie AT (2005) Identification of an intestinal heme transporter. Cell 122:789–801
Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID (2006) Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127:917–928
West AR, Oates PS (2008) Mechanisms of heme iron absorption: current questions and controversies. World J Gastroenterol 14:4101–4110
Keel SB, Doty RT, Yang Z, Quigley JG, Chen J, Knoblaugh S, Kingsley PD, De Domenico I, Vaughn MB, Kaplan J, Palis J, Abkowitz JL (2008) A heme export protein is required for red blood cell differentiation and iron homeostasis. Science 319:825–828
Sibille JC, Kondo H, Aisen P (1988) Interactions between isolated hepatocytes and Kupffer cells in iron metabolism: a possible role for ferritin as an iron carrier protein. Hepatology 8:296–301
Mack U, Cooksley WG, Ferris RA, Powell LW, Halliday JW (1981) Regulation of plasma ferritin by the isolated perfused rat liver. Br J Haematol 47:403–412
Chen TT, Li L, Chung DH, Allen CD, Torti SV, Torti FM, Cyster JG, Chen CY, Brodsky FM, Niemi EC, Nakamura MC, Seaman WE, Daws MR (2005) TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med 202:955–965
Li JY, Paragas N, Ned RM, Qiu A, Viltard M, Leete T, Drexler IR, Chen X, Sanna-Cherchi S, Mohammed F, Williams D, Lin CS, Schmidt-Ott KM, Andrews NC, Barasch J (2009) Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev Cell 16:35–46
Inman RS, Coughlan MM, Wessling-Resnick M (1994) Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport. Biochemistry 33:11850–11857
Jordan I, Kaplan J (1994) The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity. Biochem J 302:875–879
Dancis A, Klausner RD, Hinnebusch AG, Barriocanal JG (1990) Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae. Mol Cell Biol 10:2294–2301
Raja KB, Simpson RJ, Peters TJ (1992) Investigation of a role for reduction in ferric iron uptake by mouse duodenum. Biochim Biophys Acta 1135:141–146
McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, Mudaly M, Richardson C, Barlow D, Bomford A, Peters TJ, Raja KB, Shirali S, Hediger MA, Farzaneh F, Simpson RJ (2001) An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291:1755–1759
Gunshin H, Starr CN, Direnzo C, Fleming MD, Jin J, Greer EL, Sellers VM, Galica SM, Andrews NC (2005) Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood 106:2879–2883
Verrijt CE, Kroos MJ, Huijskes-Heins MI, van Eijk HG, van Dijk JP (1998) Non-transferrin iron uptake by trophoblast cells in culture. Significance of a NADH-dependent ferrireductase. Placenta 19:525–530
Knutson M, Wessling-Resnick M (2003) Iron metabolism in the reticuloendothelial system. Crit Rev Biochem Mol Biol 38:61–88
Anderson GJ, Vulpe CD (2001) Regulation of intestinal iron transport. In: Templeton DM (ed) Molecular and cellular iron transport. Marcel Dekker, New York, pp 559–596
Abboud S, Haile DJ (2000) A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 275:19906–19912
Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Lux SE, Pinkus GS, Pinkus JL, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI (2000) Postional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403:776–781
McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5:299–309
McArdle HJ, Andersen HS, Jones H, Gambling L (2008) Copper and iron transport across the placenta: regulation and interactions. J Neuroendocrinol 20:427–431
Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC (2005) The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 1:191–200
Rice AE, Mendez MJ, Hokanson CA, Rees DC, Björkman PJ (2009) Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J Mol Biol 386:717–732
De Domenico I, Ward DM, Musci G, Kaplan J (2007) Evidence for the multimeric structure of ferroportin. Blood 109:2205–2209
Quigley JG, Yang Z, Worthington MT, Phillips JD, Sabo KM, Sabath DE, Berg CL, Sassa S, Wood BL, Abkowitz JL (2004) Identification of a human heme exporter that is essential for erythropoiesis. Cell 118:757–766
Krishnamurthy P, Schuetz JD (2006) Role of ABCG2/BCRP in biology and medicine. Ann Rev Pharm Toxicol 46:381–410
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 96:10812–10817
Xu X, Pin S, Gathinji M, Fuchs R, Harris ZL (2004) Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Ann N Y Acad Sci 1012:299–305
Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ (1999) Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 21:195–199
Anderson GJ, Frazer DM, McKie AT, Vulpe CD (2002) The ceruloplasmin homolog hephaestin and the control of intestinal iron absorption. Blood Cells Mol Dis 29:367–375
Hadziahmetovic M, Dentchev T, Song Y, Haddad N, He X, Hahn P, Pratico D, Wen R, Harris ZL, Lambris J, Beard J, Dunaief J (2008) Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD. Invest Ophthalmol Vis Sci 49:2728–2736
Jeong SY, David S (2003) Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. J Biol Chem 278:27144–27148
Cherukuri S, Potla R, Sarkar J, Nurko S, Harris ZL, Fox PL (2005) Unexpected role of ceruloplasmin in intestinal iron absorption. Cell Metab 2:309–319
De Domenico I, Ward DM, di Patti MC, Jeong SY, David S, Musci G, Kaplan J (2007) Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J 26:2823–2831
Roeser HP, Lee GR, Nacht S, Cartwright GE (1970) The role of ceruloplasmin in iron metabolism. J Clin Invest 49:2408–2417
Shiono Y, Wakusawa S, Hayashi H, Takikawa T, Yano M, Okada T, Mabuchi H, Kono S, Miyajima H (2001) Iron accumulation in the liver of male patients with Wilson’s disease. Am J Gastroenterol 96:3147–3151
Kruszewski M (2003) Labile iron pool: the main determinant of cellular response to oxidative stress. Mut Res 531:81–92
Shi H, Bencze KZ, Stemmler TL, Philpott CC (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320:1207–1210
Ajioka RS, Phillips JD, Kushner JP (2006) Biosynthesis of heme in mammals. Biochim Biophys Acta 1763:723–736
Napier I, Ponka P, Richardson DR (2005) Iron trafficking in the mitochondrion: novel pathways revealed by disease. Blood 105:1867–1874
Sheftel AD, Zhang AS, Brown C, Shirihai OS, Ponka P (2007) Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 110:125–132
Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Ackermann GE, Gwynn B, Lambert AJ, Wingert RA, Traver D, Trede NS, Barut BA, Zhou Y, Minet E, Donovan A, Brownlie A, Balzan R, Weiss MJ, Peters LL, Kaplan J, Zon LI, Paw BH (2006) Mitoferrin is essential for erythroid iron assimilation. Nature 440:96–100
Paradkar PN, Zumbrennen KB, Paw BH, Ward DM, Kaplan J (2009) Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol Cell Biol 29:1007–1016
Krishnamurthy P, Xie T, Schuetz JD (2007) The role of transporters in cellular heme and porphyrin homeostasis. Pharmacol Therapeut 114:345–358
Pondarré C, Antiochos BB, Campagna DR, Clarke SL, Greer EL, Deck KM, McDonald A, Han AP, Medlock A, Kutok JL, Anderson SA, Eisenstein RS, Fleming MD (2006) The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum Mol Gene 15:953–964
Bekri S, Kispal G, Lange H, Fitzsimons E, Tolmie J, Lill R, Bishop DF (2000) Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Blood 96:3256–3264
Puccio H, Simon D, Cossée M, Criqui-Filipe P, Tiziano F, Melki J, Hindelang C, Matyas R, Rustin P, Koenig M (2001) Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet 27:181–186
Lodi R, Tonon C, Calabrese V, Schapira AH (2006) Friedreich’s ataxia: from disease mechanisms to therapeutic interventions. Antiox Redox Signal 8:438–443
Pantopoulos K (2004) Iron metabolism and the IRE/IRP regulatory system: an update. Ann N Y Acad Sci 1012:1–13
Rouault TA (2006) The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol 2:406–414
Cairo G, Recalcati S (2007) Iron-regulatory proteins: molecular biology and pathophysiological implications. Exp Rev Mol Med 9:1–13
Ponka P, Beaumont C, Richardson DR (1998) Function and regulation of transferrin and ferritin. Sem Hematol 35:35–54
Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, Hentze MW, Rouault TA, Andrews NC, Hediger MA (2001) Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett 509:309–316
Tchernitchko D, Bourgeois M, Martin M-E, Beaumont C (2002) Expression of the two mRNA isoforms of the iron transporter Nramp2/DMT1 in mice and function of the iron responsive element. Biochem J 363:449–455
Galy B, Ferring-Appel D, Kaden S, Gröne HJ, Hentze MW (2008) Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum. Cell Metab 7:79–85
Mok H, Jelinek J, Pai S, Cattanach BM, Prchal JT, Youssoufian H, Schumacher A (2004) Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemic mice. Development 131:1859–1868
Melefors O, Goossen B, Johansson HE, Stripecke R, Gray NK, Hentze MW (1993) Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells. J Biol Chem 268:5974–5978
Meyron-Holtz EG, Ghosh MC, Iwai K, LaVaute T, Brazzolotto X, Berger UV, Land W, Ollivierre-Wilson H, Grinberg A, Love P, Rouault TA (2004) Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J 23:386–395
LaVaute T, Smith S, Cooperman S, Iwai K, Land W, Meyron-Holtz E, Drake SK, Miller G, Abu-Asab M, Tsokos M, Switzer R 3rd, Grinberg A, Love P, Tresser N, Rouault TA (2001) Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet 27:209–214
Galy B, Ferring D, Minana B, Bell O, Janser HG, Muckenthaler M, Schümann K, Hentze MW (2005) Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood 106:2580–2589
Meyron-Holtz EG, Ghosh MC, Rouault TA (2004) Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306:2087–2090
Frazer DM, Vulpe CD, McKie AT, Wilkins SJ, Trinder D, Cleghorn GJ, Anderson GJ (2001) Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins. Am J Physiol 281:G931–G939
Hintze KJ, Theil EC (2006) Cellular regulation and molecular interactions of the ferritins. Cell Mol Life Sci 63:591–600
Casey JL, Di Jeso B, Rao K, Klausner RD, Harford JB (1988) Two genetic loci participate in the regulation by iron of the gene for the human transferrin receptor. Proc Natl Acad Sci USA 85:1787–1791
Peyssonnaux C, Nizet V, Johnson RS (2008) Role of the hypoxia inducible factors HIF in iron metabolism. Cell Cycle 7:28–32
Tacchini L, Bianchi L, Bernelli-Zazzera A, Cairo G (1999) Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation. J Biol Chem 274:24142–24146
Lok CN, Ponka P (1999) Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem 274:24147–24152
Weiss G (2005) Modification of iron regulation by the inflammatory response. Best Pract Res Clin Haematol 18:183–201
Trinder D, Oates PS, Thomas C, Sadlier J, Morgan EH (2000) 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 46:270–276
Scheiber-Mojdehkar B, Sturm B, Plank L, Kryzer I, Goldenberg H (2003) 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 65:1973–1978
Yeh KY, Yeh M, Watkins JA, Rodriguez-Paris J, Glass J (2000) Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression. Am J Physiol 279:G1070–G1079
Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093
Johnson MB, Chen J, Murchison N, Green FA, Enns CA (2007) Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway. Mol Biol Cell 18:743–754
Foot NJ, Dalton HE, Shearwin-Whyatt LM, Dorstyn L, Tan SS, Yang B, Kumar S (2008) Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2. Blood 112:4268–4275
Lam-Yuk-Tseung S, Gros P (2006) Distinct targeting and recycling properties of two isoforms of the iron transporter DMT1 (NRAMP2, Slc11A2). Biochemistry 45:2294–2301
De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI, Ganz T, Musci G, Kaplan J (2007) The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 18:2569–2578
De Domenico I, Lo E, Ward DM, Kaplan J (2009) Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2. Proc Natl Acad Sci USA 106:3800–3805
Wang F, Paradkar PN, Custodio AO, McVey Ward D, Fleming MD, Campagna D, Roberts KA, Boyartchuk V, Dietrich WF, Kaplan J, Andrews NC (2007) Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice. Nat Genet 39:1025–1032
Sylvester SR, Griswold MD (1994) The testicular iron shuttle: a “nurse” function of the Sertoli cells. J Androl 15:381–385
MacGillivray RTA, Mason AB (2001) Transferrins. In: Templeton DM (ed) Molecular and cellular iron transport. Marcel Dekker, New York, pp 41–69
Cairo G (2001) Regulation of liver iron metabolism. In: Templeton DM (ed) Molecular and cellular iron transport. Marcel Dekker, New York, pp 613–641
Lok CN, Loh TT (1998) Regulation of transferrin function and expression: review and update. Biol Signals Recept 7:157–178
Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98:8780–8785
Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S (2002) Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 99:4596–4601
Ganz T (2005) Hepcidin—a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol 18:171–182
Rivera S, Liu L, Nemeth E, Gabayan V, Sorensen OE, Ganz T (2005) Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia. Blood 105:1797–1802
Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276:7811–7819
Millard KN, Frazer DM, Wilkins SJ, Anderson GJ (2004) Changes in the expression of intestinal iron transport and hepatic regulatory molecules explain the enhanced iron absorption associated with pregnancy in the rat. Gut 53:655–660
Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110:1037–1044
Wang RH, Li C, Xu X, Zheng Y, Xiao C, Zerfas P, Cooperman S, Eckhaus M, Rouault T, Mishra L, Deng CX (2005) A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab 2:399–409
Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, Campagna JA, Chung RT, Schneyer AL, Woolf CJ, Andrews NC, Lin HY (2006) Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38:531–539
Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP (2009) Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet 41:478–481
Andriopoulos B Jr, Corradini E, Xia Y, Faasse SA, Chen S, Grgurevic L, Knutson MD, Pietrangelo A, Vukicevic S, Lin HY, Babitt JL (2009) BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 41:482–487
Frazer DM, Anderson GJ (2003) The orchestration of body iron intake: how and where do enterocytes receive their cues? Blood Cells Mol Dis 30:288–297
Wilkins SJ, Frazer DM, Millard KN, McLaren GD, Anderson GJ (2006) Iron metabolism in the hemoglobin-deficit mouse: correlation of diferric transferrin with hepcidin expression. Blood 107:1659–1664
Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, Nizet V, Johnson RS (2008) Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 117:1926–1932
Ahmad KA, Ahmann JR, Migas MC, Waheed A, Britton RS, Bacon BR, Sly WS, Fleming RE (2002) Decreased liver hepcidin expression in the Hfe knockout mouse. Blood Cells Mol Dis 29:361–366
Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DH, Subramaniam VN, Powell LW, Anderson GJ, Ramm GA (2003) Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361:669–673
Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, Loukopoulos D, Camaschella C (2003) Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33:21–22
Fleming RE, Britton RS, Waheed A, Sly WS, Bacon BR (2004) Pathogenesis of hereditary hemochromatosis. Clin Liver Dis 8:755–773
Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP (2004) Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 36:77–82
Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C (2005) Hepcidin is decreased in TFR2 hemochromatosis. Blood 105:1803–1806
Kemna EH, Tjalsma H, Willems HL, Swinkels DW (2008) Hepcidin: from discovery to differential diagnosis. Haematologica 93:90–97
Iacopetta BJ, Morgan EH, Yeoh GC (1982) Transferrin receptors and iron uptake during erythroid cell development. Biochim Biophys Acta 687:204–210