Regulation of cellular iron metabolism

Biochemical Journal

Volumn 434, Issue 3, 2011, Pages 365-381

  Wang, Jian ^a,b   Pantopoulos, Kostas ^a,b,c  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

Ferritin; Ferroportin; Iron regulatory protein 1 (IRP1); Iron regulatory protein 2 (IRP2); Iron sulfur cluster (ISC); Transferrin receptor (TfR)

Indexed keywords

FERRITIN; HEME; IRON; MESSENGER RNA; METAL; METALLOPROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; REGULATOR PROTEIN; TRANSFERRIN; TRANSFERRIN RECEPTOR;

CELL METABOLISM; CELL TYPE; CRYSTAL STRUCTURE; ENDOCYTOSIS; ENZYME PHOSPHORYLATION; HEME SYNTHESIS; INTESTINE CELL; IRON BALANCE; IRON METABOLISM; IRON RESPONSIVE ELEMENT; IRON TRANSPORT; MACROPHAGE; MAMMAL CELL; MITOCHONDRION; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PLASMA; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; RNA BINDING; SIGNAL TRANSDUCTION; TUMOR GROWTH;

ANIMALS; BIOLOGICAL TRANSPORT; FERRITINS; HUMANS; IRON; IRON-REGULATORY PROTEINS; MITOCHONDRIA; NEOPLASMS; OXIDATION-REDUCTION; RESPONSE ELEMENTS; RNA, MESSENGER; TRANSFERRIN;

MAMMALIA;

EID: 79952162002     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20101825     Document Type: Review

References (206)

1. Aisen, P., Enns, C. and Wessling-Resnick, M. (2001) Chemistry and biology of eukaryotic iron metabolism. Int. J. Biochem. Cell Biol. 33, 940-959
2. Koppenol, W. H. (1993) The centennial of the Fenton reaction. Free Radical Biol. Med. 15, 645-651
3. Galaris, D. and Pantopoulos, K. (2008) Oxidative stress and iron homeostasis: mechanistic and health aspects. Crit. Rev. Clin. Lab. Sci. 45, 1-23
4. Kell, D. B. (2009) Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med. Genomics 2, 2
5. De Domenico, I., McVey Ward, D. and Kaplan, J. (2008) Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat. Rev. Mol. Cell Biol. 9, 72-81
6. Hentze, M. W., Muckenthaler, M. U., Galy, B. and Camaschella, C. (2010) Two to tango: regulation of mammalian iron metabolism. Cell 142, 24-38
7. Andrews, N. C. (2008) Forging a field: the golden age of iron biology. Blood 112, 219-230
8. Andrews, N. C. (1999) Disorders of iron metabolism. N. Engl. J. Med. 341, 1986-1995
9. Olsson, K. S. and Norrby, A. (2008) Comment to: Hepcidin: from discovery to differential diagnosis. Haematologica 2008; 93:90-7. Haematologica 93, e51 (Pubitemid 351821748)
10. Yeh, K. Y., Yeh, M., Mims, L. and Glass, J. (2009) Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G55-G65
11. Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S. and Andrews, N. C. (2005) The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 1, 191-200
12. Nemeth, E. and Ganz, T. (2009) The role of hepcidin in iron metabolism. Acta Haematol. 122, 78-86
13. Lee, P. L. and Beutler, E. (2009) Regulation of hepcidin and iron-overload disease. Annu. Rev. Pathol. 4, 489-515
14. Weiss, G. and Goodnough, L. T. (2005) Anemia of chronic disease. N. Engl. J. Med. 352, 1011-1023
15. Finberg, K. E. (2009) Iron-refractory iron deficiency anemia. Semin. Hematol. 46, 378-386
16. Courselaud, B., Pigeon, C., Inoue, Y., Inoue, J., Gonzalez, F. J., Leroyer, P., Gilot, D., Boudjema, K., Guguen-Guillouzo, C., Brissot, P. 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, 41163-41170
17. Kautz, L., Meynard, D., Monnier, A., Darnaud, V., Bouvet, R., Wang, R. H., Deng, C., Vaulont, S., Mosser, J., Coppin, H. and Roth, M. P. (2008) Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 112, 1503-1509
18. Arndt, S., Maegdefrau, U., Dorn, C., Schardt, K., Hellerbrand, C. and Bosserhoff, A. K. (2010) Iron-induced expression of bone morphogenic protein 6 in intestinal cells is the main regulator of hepatic hepcidin expression in vivo. Gastroenterology 138, 372-382
19. Meynard, D., Kautz, L., Darnaud, V., Canonne-Hergaux, F., Coppin, H. and Roth, M. P. (2009) Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat. Genet. 41, 478-481
20. Andriopoulos, Jr, B., Corradini, E., Xia, Y., Faasse, S. A., Chen, S., Grgurevic, L., Knutson, M. D., Pietrangelo, A., Vukicevic, S., Lin, H. Y. and Babitt, J. L. (2009) BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat. Genet. 41, 482-487
21. Wang, R. H., Li, C., Xu, X., Zheng, Y., Xiao, C., Zerfas, P., Cooperman, S., Eckhaus, M., Rouault, T., Mishra, L. and Deng, C. X. (2005) A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab. 2, 399-409
22. Gao, J., Chen, J., Kramer, M., Tsukamoto, H., Zhang, A. S. and Enns, C. A. (2009) Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab. 9, 217-227
23. Ramey, G., Deschemin, J. C. and Vaulont, S. (2009) Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes. Haematologica 94, 765-772
24. Silvestri, L., Pagani, A., Nai, A., De Domenico, I., Kaplan, J. and Camaschella, C. (2008) The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 8, 502-511
25. Fleming, R. E. (2008) Iron and inflammation: cross-talk between pathways regulating hepcidin. J. Mol. Med. 86, 491-494
26. Matak, P., Chaston, T. B., Chung, B., Srai, S. K., McKie, A. T. and Sharp, P. A. (2009) Activated macrophages induce hepcidin expression in HuH7 hepatoma cells. Haematologica 94, 773-780
27. Vecchi, C., Montosi, G., Zhang, K., Lamberti, I., Duncan, S. A., Kaufman, R. J. and Pietrangelo, A. (2009) ER stress controls iron metabolism through induction of hepcidin. Science 325, 877-880
28. Oliveira, S. J., Pinto, J. P., Picarote, G., Costa, V. M., Carvalho, F., Rangel, M., de Sousa, M. and de Almeida, S. F. (2009) ER stress-inducible factor CHOP affects the expression of hepcidin by modulating C/EBPα activity. PLoS ONE 4, e6618
29. Peyssonnaux, C., Zinkernagel, A. S., Datta, V., Lauth, X., Johnson, R. S. and Nizet, V. (2006) TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 107, 3727-3732
30. Koening, C. L., Miller, J. C., Nelson, J. M., Ward, D. M., Kushner, J. P., Bockenstedt, L. K., Weis, J. J., Kaplan, J. and De Domenico, I. (2009) Toll-like receptors mediate induction of hepcidin in mice infected with Borrelia burgdorferi. Blood 114, 1913-1918
31. Pak, M., Lopez, M. A., Gabayan, V., Ganz, T. and Rivera, S. (2006) Suppression of hepcidin during anemia requires erythropoietic activity. Blood 108, 3730-3735 (Pubitemid 44864551)
32. Tanno, T., Bhanu, N. V., Oneal, P. A., Goh, S. H., Staker, P., Lee, Y. T., Moroney, J. W., Reed, C. H., Luban, N. L., Wang, R. H. et al. (2007) High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat. Med. 13, 1096-1101
33. Tanno, T., Porayette, P., Sripichai, O., Noh, S. J., Byrnes, C., Bhupatiraju, A., Lee, Y. T., Goodnough, J. B., Harandi, O., Ganz, T. et al. (2009) Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 114, 181-186
34. Pinto, J. P., Ribeiro, S., Pontes, H., Thowfeequ, S., Tosh, D., Carvalho, F. and Porto, G. (2008) Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPα. Blood 111, 5727-5733
35. Volke, M., Gale, D. P., Maegdefrau, U., Schley, G., Klanke, B., Bosserhoff, A. K., Maxwell, P. H., Eckardt, K. U. and Warnecke, C. (2009) Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors. PLoS ONE 4, e7875
36. Miura, K., Taura, K., Kodama, Y., Schnabl, B. and Brenner, D. A. (2008) Hepatitis C virus-induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity. Hepatology 48, 1420-1429
37. Ludwiczek, S., Aigner, E., Theurl, I. and Weiss, G. (2003) Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 101, 4148-4154 (Pubitemid 36857898)
38. Vanoaica, L., Darshan, D., Richman, L., Schumann, K. and Kuhn, L. C. (2010) Intestinal ferritin H is required for an accurate control of iron absorption. Cell Metab. 12, 273-282
39. Shah, Y. M., Matsubara, T., Ito, S., Yim, S. H. and Gonzalez, F. J. (2009) Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab. 9, 152-164
40. Mastrogiannaki, M., Matak, P., Keith, B., Simon, M. C., Vaulont, S. and Peyssonnaux, C. (2009) HIF-2α, but not HIF-1α, promotes iron absorption in mice. J. Clin. Invest. 119, 1159-1166
41. Ponka, P., Beaumont, C. and Richardson, D. R. (1998) Function and regulation of transferrin and ferritin. Semin. Hematol. 35, 35-54
42. Ohgami, R. S., Campagna, D. R., Greer, E. L., Antiochos, B., McDonald, A., Chen, J., Sharp, J. J., Fujiwara, Y., Barker, J. E. and Fleming, M. D. (2005) Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat. Genet. 37, 1264-1269
43. Richardson, D. R., Lane, D. J., Becker, E. M., Huang, M. L., Whitnall, M., Rahmanto, Y. S., Sheftel, A. D. and Ponka, P. (2010) Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol. Proc. Natl. Acad. Sci. U.S.A. 107, 10775-10782
44. Levy, J. E., Jin, O., Fujiwara, Y., Kuo, F. and Andrews, N. C. (1999) Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat. Genet. 21, 396-399
45. Trenor, C. C., Campagna, D. R., Sellers, V. M., Andrews, N. C. and Fleming, M. D. (2000) The molecular defect in hypotransferrinemic mice. Blood 96, 1113-1118
46. Gunshin, H., Fujiwara, Y., Custodio, A. O., Direnzo, C., Robine, S. and Andrews, N. C. (2005) Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J. Clin. Invest. 115, 1258-1266
47. Fleming, M. D., Trenor, C. C. I., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F. and Andrews, N. C. (1997) Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat. Genet. 16, 383-386
48. Fleming, M. D., Romano, M. A., Su, M. A., Garrick, L. M., Garrick, M. D. and Andrews, N. C. (1998) 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. 95, 1148-1153
49. Kristiansen, M., Graversen, J. H., Jacobsen, C., Sonne, O., Hoffman, H. J., Law, S. K. and Moestrup, S. K. (2001) Identification of the haemoglobin scavenger receptor. Nature 409, 198-201
50. Hvidberg, V., Maniecki, M. B., Jacobsen, C., Hojrup, P., Moller, H. J. and Moestrup, S. K. (2005) Identification of the receptor scavenging hemopexin-heme complexes. Blood 106, 2572-2579
51. Soe-Lin, S., Apte, S. S., Andriopoulos, B., Jr., Andrews, M. C., Schranzhofer, M., Kahawita, T., Garcia-Santos, D. and Ponka, P. (2009) Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc. Natl. Acad. Sci. U.S.A. 106, 5960-5965
52. Zecca, L., Youdim, M. B., Riederer, P., Connor, J. R. and Crichton, R. R. (2004) Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci. 5, 863-873
53. Rouault, T. A., Zhang, D. L. and Jeong, S. Y. (2009) Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins. Metab. Brain Dis. 24, 673-684
54. Jeong, S. Y. and David, S. (2003) Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. J. Biol. Chem. 278, 27144-27148
55. Duce, J. A., Tsatsanis, A., Cater, M. A., James, S. A., Robb, E., Wikhe, K., Leong, S. L., Perez, K., Johanssen, T., Greenough, M. A. et al. (2010) Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell 142, 857-867
56. Smith, C. P. and Thevenod, F. (2009) Iron transport and the kidney. Biochim. Biophys. Acta 1790, 724-730
57. Kozyraki, R., Fyfe, J., Verroust, P. J., Jacobsen, C., Dautry-Varsat, A., Gburek, J., Willnow, T. E., Christensen, E. I. and Moestrup, S. K. (2001) Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc. Natl. Acad. Sci. U.S.A. 98, 12491-12496
58. Goetz, D. H., Holmes, M. A., Borregaard, N., Bluhm, M. E., Raymond, K. N. and Strong, R. K. (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell 10, 1033-1043
59. Yang, J., Goetz, D., Li, J. Y., Wang, W., Mori, K., Setlik, D., Du, T., Erdjument-Bromage, H., Tempst, P., Strong, R. and Barasch, J. (2002) An iron delivery pathway mediated by a lipocalin. Mol. Cell 10, 1045-1056 (Pubitemid 35453824)
60. Mori, K., Lee, H. T., Rapoport, D., Drexler, I. R., Foster, K., Yang, J., Schmidt-Ott, K. M., Chen, X., Li, J. Y., Weiss, S. et al. (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J. Clin. Invest. 115, 610-621
61. Devireddy, L. R., Gazin, C., Zhu, X. and Green, M. R. (2005) A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 123, 1293-1305
62. Hvidberg, V., Jacobsen, C., Strong, R. K., Cowland, J. B., Moestrup, S. K. and Borregaard, N. (2005) The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett. 579, 773-777
63. Devireddy, L. R., Hart, D. O., Goetz, D. H. and Green, M. R. (2010) A mammalian siderophore synthesized by an enzyme with a bacterial homolog involved in enterobactin production. Cell 141, 1006-1017
64. Flo, T. H., Smith, K. D., Sato, S., Rodriguez, D. J., Holmes, M. A., Strong, R. K., Akira, S. and Aderem, A. (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917-921 (Pubitemid 40037155)
65. Breuer, W., Hershko, C. and Cabantchik, Z. I. (2000) The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus. Sci. 23, 185-192
66. Hider, R. C. (2002) Nature of nontransferrin-bound iron. Eur. J. Clin. Invest. 32 (Suppl. 1), 50-54
67. Huang, H., Akira, S. and Santos, M. M. (2009) Is the iron donor lipocalin 2 implicated in the pathophysiology of hereditary hemochromatosis? Hepatology 49, 1012-1016
68. Liuzzi, J. P., Aydemir, F., Nam, H., Knutson, M. D. and Cousins, R. J. (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc. Natl. Acad. Sci. U.S.A. 103, 13612-13617
69. Zhao, N., Gao, J., Enns, C. A. and Knutson, M. D. (2010) ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. J. Biol. Chem. 285, 32141-32150
70. Chen, T. T., Li, L., Chung, D. H., Allen, C. D., Torti, S. V., Torti, F. M., Cyster, J. G., Chen, C. Y., Brodsky, F. M., Niemi, E. C. et al. (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
71. Li, J. Y., Paragas, N., Ned, R. M., Qiu, A., Viltard, M., Leete, T., Drexler, I. R., Chen, X., Sanna-Cherchi, S., Mohammed, F. et al. (2009) Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev. Cell 16, 35-46
72. Li, L., Fang, C. J., Ryan, J. C., Niemi, E. C., Lebron, J. A., Bjorkman, P. J., Arase, H., Torti, F. M., Torti, S. V., Nakamura, M. C. and Seaman, W. E. (2010) Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc. Natl. Acad. Sci. U.S.A. 107, 3505-3510
73. Muhlenhoff, U., Molik, S., Godoy, J. R., Uzarska, M. A., Richter, N., Seubert, A., Zhang, Y., Stubbe, J., Pierrel, F., Herrero, E. et al. (2010) Cytosolic monothiol glutaredoxins function in intracellular iron sensing and trafficking via their bound iron-sulfur cluster. Cell Metab. 12, 373-385
74. Shaw, G. C., Cope, J. J., Li, L., Corson, K., Hersey, C., Ackermann, G. E., Gwynn, B., Lambert, A. J., Wingert, R. A., Traver, D. et al. (2006) Mitoferrin is essential for erythroid iron assimilation. Nature 440, 96-100 (Pubitemid 43336274)
75. Chen, W., Paradkar, P. N., Li, L., Pierce, E. L., Langer, N. B., Takahashi-Makise, N., Hyde, B. B., Shirihai, O. S., Ward, D. M., Kaplan, J. and Paw, B. H. (2009) Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. Proc. Natl. Acad. Sci. U.S.A. 106, 16263-16268
76. Paradkar, P. N., Zumbrennen, K. B., Paw, B. H., Ward, D. M. and Kaplan, J. (2009) Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol. Cell. Biol. 29, 1007-1016
77. Severance, S. and Hamza, I. (2009) Trafficking of heme and porphyrins in metazoa. Chem. Rev. 109, 4596-4616
78. Ryter, S. W. and Tyrrell, R. M. (2000) The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. Free Radical Biol. Med. 28, 289-309
79. Ponka, P. (1997) Tissue-specific regulation of iron metabolism and heme synthesis: distinct control mechanisms in erythroid cells. Blood 89, 1-25
80. Nilsson, R., Schultz, I. J., Pierce, E. L., Soltis, K. A., Naranuntarat, A., Ward, D. M., Baughman, J. M., Paradkar, P. N., Kingsley, P. D., Culotta, V. C. et al. (2009) Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis. Cell Metab. 10, 119-130
81. Johnson, D. C., Dean, D. R., Smith, A. D. and Johnson, M. K. (2005) Structure, function, and formation of biological iron-sulfur clusters. Annu. Rev. Biochem. 74, 247-281
82. Lill, R. (2009) Function and biogenesis of iron-sulphur proteins. Nature 460, 831-838
83. Ye, H. and Rouault, T. A. (2010) Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry 49, 4945-4956
84. Netz, D. J., Pierik, A. J., Stumpfig, M., Muhlenhoff, U. and Lill, R. (2007) The Cfd1-Nbp35 complex acts as a scaffold for iron-sulfur protein assembly in the yeast cytosol. Nat. Chem. Biol. 3, 278-286
85. Keel, S. B., Doty, R. T., Yang, Z., Quigley, J. G., Chen, J., Knoblaugh, S., Kingsley, P. D., De Domenico, I., Vaughn, M. B. and Kaplan, J. (2008) A heme export protein is required for red blood cell differentiation and iron homeostasis. Science 319, 825-828 (Pubitemid 351225875)
86. Arosio, P., Ingrassia, R. and Cavadini, P. (2009) Ferritins: a family of molecules for iron storage, antioxidation and more. Biochim. Biophys. Acta 1790, 589-599
87. Shi, H., Bencze, K. Z., Stemmler, T. L. and Philpott, C. C. (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320, 1207-1210
88. Zhang, Y., Mikhael, M., Xu, D., Li, Y., Soe-Lin, S., Ning, B., Li, W., Nie, G., Zhao, Y. and Ponka, P. (2010) Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit. Antioxid. Redox Signaling 13, 999-1009
89. Takagi, H., Shi, D., Ha, Y., Allewell, N. M. and Theil, E. C. (1998) Localized unfolding at the junction of three ferritin subunits. A mechanism for iron release? J. Biol. Chem. 273, 18685-18688
90. Mikhael, M., Sheftel, A. D. and Ponka, P. (2010) Ferritin does not donate its iron for haem synthesis in macrophages. Biochem. J. 429, 463-471
91. De Domenico, I., Vaughn, M. B., Li, L., Bagley, D., Musci, G., Ward, D. M. and Kaplan, J. (2006) Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J. 25, 5396-5404 (Pubitemid 44764148)
92. De Domenico, I., Ward, D. M. and Kaplan, J. (2009) Specific iron chelators determine the route of ferritin degradation. Blood 114, 4546-4551
93. Ferreira, C., Bucchini, D., Martin, M. E., Levi, S., Arosio, P., Grandchamp, B. and Beaumont, C. (2000) Early embryonic lethality of H ferritin gene deletion in mice. J. Biol. Chem. 275, 3021-3024
94. Darshan, D., Vanoaica, L., Richman, L., Beermann, F. and Kuhn, L. C. (2009) Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage. Hepatology 50, 852-860
95. Levi, S., Cozzi, A. and Arosio, P. (2005) Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin mutation. Best Pract. Res. Clin. Haematol. 18, 265-276
96. Levi, S. and Arosio, P. (2004) Mitochondrial ferritin. Int. J. Biochem. Cell Biol. 36, 1887-1889
97. Cazzola, M., Invernizzi, R., Bergamaschi, G., Levi, S., Corsi, B., Travaglino, E., Rolandi, V., Biasiotto, G., Drysdale, J. and Arosio, P. (2003) Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood 101, 1996-2000 (Pubitemid 36237606)
98. Cohen, L. A., Gutierrez, L., Weiss, A., Leichtmann-Bardoogo, Y., Zhang, D. L., Crooks, D. R., Sougrat, R., Morgenstern, A., Galy, B., Hentze, M. W. et al. (2010) Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 116, 1574-1584
99. Breuer, W., Shvartsman, M. and Cabantchik, Z. I. (2008) Intracellular labile iron. Int. J. Biochem. Cell Biol. 40, 350-354
100. Petrat, F., de Groot, H., Sustmann, R. and Rauen, U. (2002) The chelatable iron pool in living cells: a methodically defined quantity. Biol. Chem. 383, 489-502
101. Rauen, U., Springer, A., Weisheit, D., Petrat, F., Korth, H. G., de Groot, H. and Sustmann, R. (2007) Assessment of chelatable mitochondrial iron by using mitochondrion-selective fluorescent iron indicators with different iron-binding affinities. ChemBioChem 8, 341-352 (Pubitemid 47194515)
102. Epsztejn, S., Glickstein, H., Picard, V., Slotki, I. N., Breuer, W., Beaumont, C. and Cabantchik, Z. I. (1999) H-Ferritin subunit overexpression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood 94, 3593-3603
103. Kaur, D., Yantiri, F., Rajagopalan, S., Kumar, J., Mo, J. Q., Boonplueang, R., Viswanath, V., Jacobs, R., Yang, L., Beal, M. F. 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 (Pubitemid 36398297)
104. Kaur, D., Rajagopalan, S. and Andersen, J. K. (2009) Chronic expression of H-ferritin in dopaminergic midbrain neurons results in an age-related expansion of the labile iron pool and subsequent neurodegeneration: implications for Parkinson's disease. Brain Res. 1297, 17-22
105. Rouault, T. A. (2006) The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat. Chem. Biol. 2, 406-414
106. Recalcati, S., Minotti, G. and Cairo, G. (2010) Iron regulatory proteins: from molecular mechanisms to drug development. Antioxid. Redox Signaling 13, 1593-1616
107. Wallander, M. L., Leibold, E. A. and Eisenstein, R. S. (2006) Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim. Biophys. Acta 1763, 668-689
108. Piccinelli, P. and Samuelsson, T. (2007) Evolution of the iron-responsive element. RNA 13, 952-966 (Pubitemid 46984887)
109. Roetto, A., Bosio, S., Gramaglia, E., Barilaro, M. R., Zecchina, G. and Camaschella, C. (2002) Pathogenesis of hyperferritinemia cataract syndrome. Blood Cells Mol. Dis. 29, 532-535
110. Schranzhofer, M., Schifrer, M., Cabrera, J. A., Kopp, S., Chiba, P., Beug, H. and Mullner, E. W. (2006) Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis. Blood 107, 4159-4167
111. Lok, C. N. and Ponka, P. (2000) Identification of an erythroid active element in the transferrin receptor gene. J. Biol. Chem. 275, 24185-24190
112. Torti, F. M. and Torti, S. V. (2002) Regulation of ferritin genes and protein. Blood 99, 3505-3516
113. Ponka, P. and Lok, C. N. (1999) The transferrin receptor: role in health and disease. Int. J. Biochem. Cell Biol. 31, 1111-1137
114. Wingert, R. A., Galloway, J. L., Barut, B., Foott, H., Fraenkel, P., Axe, J. L., Weber, G. J., Dooley, K., Davidson, A. J., Schmidt, B. et al. (2005) Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436, 1035-1039 (Pubitemid 41191688)
115. Ye, H., Jeong, S. Y., Ghosh, M. C., Kovtunovych, G., Silvestri, L., Ortillo, D., Uchida, N., Tisdale, J., Camaschella, C. and Rouault, T. A. (2010) Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J. Clin. Invest. 120, 1749-1761
116. Hubert, N. and Hentze, M. W. (2002) Previously uncharacterized isoforms of divalent metal transporter (DMT)- 1: implications for regulation and cellular function. Proc. Natl. Acad. Sci. U.S.A. 99, 12345-12350
117. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L. and Hediger, M. A. (1997) Cloning and characterization of a mammalian protein-coupled metal-ion transporter. Nature 388, 482-488
118. Zhang, D. L., Hughes, R. M., Ollivierre-Wilson, H., Ghosh, M. C. and Rouault, T. A. (2009) A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression. Cell Metab. 9, 461-473
119. Abboud, S. and Haile, D. J. (2000) A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275, 19906-19912
120. McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F. 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 (Pubitemid 30628088)
121. Mok, H., Jelinek, J., Pai, S., Cattanach, B. M., Prchal, J. T., Youssoufian, H. and Schumacher, A. (2004) Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice. Development 131, 1859-1868 (Pubitemid 38559852)
122. Sanchez, M., Galy, B., Muckenthaler, M. U. and Hentze, M. W. (2007) Iron-regulatory proteins limit hypoxia-inducible factor-2α expression in iron deficiency. Nat. Struct. Mol. Biol. 14, 420-426
123. Zimmer, M., Ebert, B. L., Neil, C., Brenner, K., Papaioannou, I., Melas, A., Tolliday, N., Lamb, J., Pantopoulos, K., Golub, T. and Iliopoulos, O. (2008) Small-molecule inhibitors of HIF-2a translation link its 5′UTR iron-responsive element to oxygen sensing. Mol. Cell 32, 838-848
124. 12,14- prostaglandin J2. Cancer Res. 70, 3071-3079
125. Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B. and Haase, V. H. (2007) Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J. Clin. Invest. 117, 1068-1077
126. Gruber, M., Hu, C. J., Johnson, R. S., Brown, E. J., Keith, B. and Simon, M. C. (2007) Acute postnatal ablation of Hif-2α results in anemia. Proc. Natl. Acad. Sci. U.S.A. 104, 2301-2306
127. Cmejla, R., Petrak, J. and Cmejlova, J. (2006) A novel iron responsive element in the 3′UTR of human MRCKα. Biochem. Biophys. Res. Commun. 341, 158-166
128. Sanchez, M., Galy, B., Dandekar, T., Bengert, P., Vainshtein, Y., Stolte, J., Muckenthaler, M. U. and Hentze, M. W. (2006) Iron regulation and the cell cycle: identification of an iron-responsive element in the 3′-untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategy. J. Biol. Chem. 281, 22865-22874
129. Cho, H. H., Cahill, C. M., Vanderburg, C. R., Scherzer, C. R., Wang, B., Huang, X. and Rogers, J. T. (2010) Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1. J. Biol. Chem. 285, 31217-31232
130. Friedlich, A. L., Tanzi, R. E. and Rogers, J. T. (2007) The 5′-untranslated region of Parkinson's disease α-synuclein messenger RNA contains a predicted iron responsive element. Mol. Psychiatry 12, 222-223
131. Tang, Y. and Guest, J. R. (1999) Direct evidence for mRNA binding and post-transcriptional regulation by Escherichia coli aconitases. Microbiology 145, 3069-3079
132. Alen, C. and Sonenshein, A. L. (1999) Bacillus subtilis aconitase is an RNA-binding protein. Proc. Natl. Acad. Sci. U.S.A. 96, 10412-10417
133. Dandekar, T., Beyer, K., Bork, P., Kenealy, M. -R., Pantopoulos, K., Hentze, M. W., Sonntag-Buck, V., Flouriot, G., Gannon, F., Keller, W. and Schreiber, S. (1998) Systematic genomic screening and analysis of mRNA in untranslated regions and mRNA precursors: combining experimental and computational approaches. Bioinformatics 14, 271-278 (Pubitemid 28395863)
134. Gruer, M. J., Artymiuk, P. J. and Guest, J. R. (1997) The aconitase family: three structural variations on a common theme. Trends Biochem. Sci. 22, 3-6
135. Dycke, C., Bougault, C., Gaillard, J., Andrieu, J. P., Pantopoulos, K. and Moulis, J. M. (2007) Human iron regulatory protein 2 is easily cleaved in its specific domain: consequences for the heme binding properties of the protein. Biochem. J. 408, 429-439
136. Dupuy, J., Volbeda, A., Carpentier, P., Darnault, C., Moulis, J. M. and Fontecilla-Camps, J. C. (2006) Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Structure 14, 129-139
137. Walden, W. E., Selezneva, A. I., Dupuy, J., Volbeda, A., Fontecilla-Camps, J. C., Theil, E. C. and Volz, K. (2006) Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA. Science 314, 1903-1908 (Pubitemid 46026108)
138. Zumbrennen, K. B., Wallander, M. L., Romney, S. J. and Leibold, E. A. (2009) Cysteine oxidation regulates the RNA-binding activity of iron regulatory protein 2. Mol. Cell. Biol. 29, 2219-2229
139. Fillebeen, C., Caltagirone, A., Martelli, A., Moulis, J. M. and Pantopoulos, K. (2005) IRP1 Ser-711 is a phosphorylation site, critical for regulation of RNA-binding and aconitase activities. Biochem. J. 388, 143-150 (Pubitemid 40732941)
140. Biederbick, A., Stehling, O., Rösser, R., Niggemeyer, B., Nakai, Y., Elsässer, H. P. and Lill, R. (2006) Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation. Mol. Cell. Biol. 26, 5675-5687
141. Fosset, C., Chauveau, M. J., Guillon, B., Canal, F., Drapier, J. C. and Bouton, C. (2006) RNA silencing of mitochondrial m-Nfs1 reduces Fe-S enzyme activity both in mitochondria and cytosol of mammalian cells. J. Biol. Chem. 281, 25398-25406
142. Wang, J., Fillebeen, C., Chen, G., Biederbick, A., Lill, R. and Pantopoulos, K. (2007) Iron-dependent degradation of apo-IRP1 by the ubiquitin-proteasome pathway. Mol. Cell. Biol. 27, 2423-2430
143. Stehling, O., Elsasser, H. P., Bruckel, B., Muhlenhoff, U. and Lill, R. (2004) Iron-sulfur protein maturation in human cells: evidence for a function of frataxin. Hum. Mol. Genet. 13, 3007-3015
144. Seznec, H., Simon, D., Bouton, C., Reutenauer, L., Hertzog, A., Golik, P., Procaccio, V., Patel, M., Drapier, J. C., Koenig, M. and Puccio, H. (2005) Friedreich ataxia: the oxidative stress paradox. Hum. Mol. Genet. 14, 463-474
145. Tong, W. H. and Rouault, T. A. (2006) Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab. 3, 199-210
146. Shi, Y., Ghosh, M., Tong, W. H. and Rouault, T. A. (2009) Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis. Hum. Mol. Genet. 18, 3014-3025
147. Pondarre, C., Antiochos, B. B., Campagna, D. R., Clarke, S. L., Greer, E. L., Deck, K. M., McDonald, A., Han, A. P., Medlock, A., Kutok, J. L. et al. (2006) The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum. Mol. Genet. 15, 953-964
148. Bouton, C., Chauveau, M. J., Lazereg, S. and Drapier, J. C. (2002) Recycling of RNA binding iron regulatory protein 1 into an aconitase after nitric oxide removal depends on mitochondrial ATP. J. Biol. Chem. 277, 31220-31227
149. Popovic, Z. and Templeton, D. M. (2010) Interaction of iron regulatory protein-1 (IRP-1) with ATP/ADP maintains a non-IRE-binding state. Biochem. J. 430, 315-324
150. Li, K., Tong, W. H., Hughes, R. M. and Rouault, T. A. (2006) Roles of the mammalian cytosolic cysteine desulfurase, ISCS, and scaffold protein, ISCU, in iron-sulfur cluster assembly. J. Biol. Chem. 281, 12344-12351
151. Roy, A., Solodovnikova, N., Nicholson, T., Antholine, W. and Walden, W. E. (2003) A novel eukaryotic factor for cytosolic Fe-S cluster assembly. EMBO J. 22, 4826-4835
152. Stehling, O., Netz, D. J., Niggemeyer, B., Rosser, R., Eisenstein, R. S., Puccio, H., Pierik, A. J. and Lill, R. (2008) Human Nbp35 is essential for both cytosolic iron-sulfur protein assembly and iron homeostasis. Mol. Cell. Biol. 28, 5517-5528
153. Song, D. and Lee, F. S. (2008) A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis. J. Biol. Chem. 283, 9231-9238
154. Balk, J., Aguilar Netz, D. J., Tepper, K., Pierik, A. J. and Lill, R. (2005) The essential WD40 protein Cia1 is involved in a late step of cytosolic and nuclear iron-sulfur protein assembly. Mol. Cell. Biol. 25, 10833-10841
155. Zhang, Y., Lyver, E. R., Nakamaru-Ogiso, E., Yoon, H., Amutha, B., Lee, D. W., Bi, E., Ohnishi, T., Daldal, F., Pain, D. and Dancis, A. (2008) Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis. Mol. Cell. Biol. 28, 5569-5582
156. Netz, D. J., Stumpfig, M., Dore, C., Muhlenhoff, U., Pierik, A. J. and Lill, R. (2010) Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur
157. Clarke, S. L., Vasanthakumar, A., Anderson, S. A., Pondarre, C., Koh, C. M., Deck, K. M., Pitula, J. S., Epstein, C. J., Fleming, M. D. and Eisenstein, R. S. (2006) Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe-S cluster. EMBO J. 25, 544-553 (Pubitemid 43237661)
158. Fillebeen, C., Chahine, D., Caltagirone, A., Segal, P. and Pantopoulos, K. (2003) A phosphomimetic mutation at Ser-138 renders iron regulatory protein 1 sensitive to iron-dependent degradation. Mol. Cell. Biol. 23, 6973-6981
159. Meyron-Holtz, E. G., Ghosh, M. C. and Rouault, T. A. (2004) Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306, 2087-2090
160. Deck, K. M., Vasanthakumar, A., Anderson, S. A., Goforth, J. B., Kennedy, M. C., Antholine, W. E. and Eisenstein, R. S. (2009) Evidence that phosphorylation of iron regulatory protein 1 at serine 138 destabilizes the [4Fe-4S] cluster in cytosolic aconitase by enhancing 4Fe-3Fe cycling. J. Biol. Chem. 284, 12701-12709
161. Pitula, J. S., Deck, K. M., Clarke, S. L., Anderson, S. A., Vasanthakumar, A. and Eisenstein, R. S. (2004) Selective inhibition of the citrate-to-isocitrate reaction of cytosolic aconitase by phosphomimetic mutation of serine-711. Proc. Natl. Acad. Sci. U.S.A. 101, 10907-10912
162. Patton, S. M., Pinero, D. J., Surguladze, N., Beard, J. and Connor, J. R. (2005) Subcellular localization of iron regulatory proteins to Golgi and ER membranes. J. Cell Sci. 118, 4365-4373
163. Hanson, E. S., Rawlins, M. L. and Leibold, E. A. (2003) Oxygen and iron regulation of iron regulatory protein 2. J. Biol. Chem. 278, 40337-40342
164. Wang, J., Chen, G., Muckenthaler, M., Galy, B., Hentze, M. W. and Pantopoulos, K. (2004) Iron-mediated degradation of IRP2: an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity. Mol. Cell. Biol. 24, 954-965
165. Wang, J., Chen, G., Lee, J. and Pantopoulos, K. (2008) Iron-dependent degradation of IRP2 requires its C-terminal region and IRP structural integrity. BMC Mol. Biol. 9, 15
166. Bourdon, E., Kang, D. K., Ghosh, M. C., Drake, S. K., Wey, J., Levine, R. L. and Rouault, T. A. (2003) The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2. Blood Cells Mol. Dis. 31, 247-255
167. Wang, J., Fillebeen, C., Chen, G., Andriopoulos, B. and Pantopoulos, K. (2006) Sodium nitroprusside promotes IRP2 degradation via an increase in intracellular iron and in the absence of S-nitrosylation at C178. Mol. Cell. Biol. 26, 1948-1954
168. Kim, S., Wing, S. S. and Ponka, P. (2004) S-nitrosylation of IRP2 regulates its stability via the ubiquitin-proteasome pathway. Mol. Cell. Biol. 24, 330-337
169. Vashisht, A. A., Zumbrennen, K. B., Huang, X., Powers, D. N., Durazo, A., Sun, D., Bhaskaran, N., Persson, A., Uhlen, M., Sangfelt, O. et al. (2009) Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science 326, 718-721
170. Salahudeen, A. A., Thompson, J. W., Ruiz, J. C., Ma, H. W., Kinch, L. N., Li, Q., Grishin, N. V. and Bruick, R. K. (2009) An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science 326, 722-726
171. French, C. E., Bell, J. M. and Ward, F. B. (2008) Diversity and distribution of hemerythrin-like proteins in prokaryotes. FEMS Microbiol. Lett. 279, 131-145
172. Wallander, M. L., Zumbrennen, K. B., Rodansky, E. S., Romney, S. J. and Leibold, E. A. (2008) Iron-independent phosphorylation of iron regulatory protein 2 regulates ferritin during the cell cycle. J. Biol. Chem. 283, 23589-23598
173. Fillebeen, C. and Pantopoulos, K. (2002) Redox control of iron regulatory proteins. Redox Rep. 7, 15-22 (Pubitemid 34285103)
174. Mütze, S., Hebling, U., Stremmel, W., Wang, J., Arnhold, J., Pantopoulos, K. and Mueller, S. (2003) Myeloperoxidase-derived hypochlorous acid antagonizes the oxidative stress-mediated activation of iron regulatory protein 1. J. Biol. Chem. 278, 40542-40549
175. Watts, R. N., Hawkins, C., Ponka, P. and Richardson, D. R. (2006) Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1. Proc. Natl. Acad. Sci. U.S.A. 103, 7670-7675
176. Wang, J., Chen, G. and Pantopoulos, K. (2005) Nitric oxide inhibits the degradation of IRP2. Mol. Cell. Biol. 25, 1347-1353
177. 176a Hausmann, A., Lee, J. and Pantopoulos, K. (2011) Redox control of iron regulatory protein 2 stability. FEBS Lett., doi:10.1016/j.febslet.2011.01. 036
178. Caltagirone, A., Weiss, G. and Pantopoulos, K. (2001) Modulation of cellular iron metabolism by hydrogen peroxide. Effects of H2O2 on the expression and function of iron-responsive element-containing mRNAs in B6 fibroblasts. J. Biol. Chem. 276, 19738-19745
179. Andriopoulos, B., Hegedusch, S., Mangin, J., Riedel, H. D., Hebling, U., Wang, J., Pantopoulos, K. and Mueller, S. (2007) Sustained hydrogen peroxide induces iron uptake by transferrin receptor-1 independent of the IRP/IRE network. J. Biol. Chem. 282, 20301-20308
180. Mehlhase, J., Sandig, G., Pantopoulos, K. and Grune, T. (2005) Oxidation-induced ferritin turnover in microglial cells: role of proteasome. Free Radical Biol. Med. 38, 276-285
181. Gerald, D., Berra, E., Frapart, Y. M., Chan, D. A., Giaccia, A. J., Mansuy, D., Pouyssegur, J., Yaniv, M. and Mechta-Grigoriou, F. (2004) JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 118, 781-794 (Pubitemid 39221736)
182. Salahudeen, A. A. and Bruick, R. K. (2009) Maintaining Mammalian iron and oxygen homeostasis: sensors, regulation, and cross-talk. Ann. N. Y. Acad. Sci. 1177, 30-38
183. Hofer, T., Wenger, R. H., Kramer, M. F., Ferreira, G. C. and Gassmann, M. (2003) Hypoxic up-regulation of erythroid 5-aminolevulinate synthase. Blood 101, 348-350 (Pubitemid 36025930)
184. Choi, S. O., Cho, Y. S., Kim, H. L. and Park, J. W. (2007) ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPα and STAT-3. Biochem. Biophys. Res. Commun. 356, 312-317
185. Harrison-Findik, D. D., Schafer, D., Klein, E., Timchenko, N. A., Kulaksiz, H., Clemens, D., Fein, E., Andriopoulos, B., Pantopoulos, K. and Gollan, J. (2006) Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J. Biol. Chem. 281, 22974-22982
186. Smith, S. R., Ghosh, M. C., Ollivierre-Wilson, H., Hang Tong, W. and Rouault, T. A. (2006) Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development. Blood Cells Mol. Dis. 36, 283-287
187. Galy, B., Ferring-Appel, D., Kaden, S., Grone, H. J. and Hentze, M. W. (2008) Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum. Cell Metab. 7, 79-85
188. Galy, B., Ferring-Appel, D., Sauer, S. W., Kaden, S., Lyoumi, S., Puy, H., Kolker, S., Grone, H. J. and Hentze, M. W. (2010) Iron regulatory proteins secure mitochondrial iron sufficiency and function. Cell Metab. 12, 194-201
189. Muckenthaler, M. U., Galy, B. and Hentze, M. W. (2008) Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu. Rev. Nutr. 28, 197-213
190. Meyron-Holtz, E. G., Ghosh, M. C., Iwai, K., LaVaute, T., Brazzolotto, X., Berger, U. V., Land, W., Ollivierre-Wilson, H., Grinberg, A., Love, P. and Rouault, T. A. (2004) Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J. 23, 386-395
191. Viatte, L., Grone, H. J., Hentze, M. W. and Galy, B. (2009) In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation. J. Mol. Med. 87, 913-921
192. Corna, G., Galy, B., Hentze, M. W. and Cairo, G. (2006) IRP1-independent alterations of cardiac iron metabolism in doxorubicin-treated mice. J. Mol. Med. 84, 551-560
193. Tong, W. H. and Rouault, T. A. (2007) Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur cluster biogenesis. Biometals 20, 549-564
194. Cooperman, S. S., Meyron-Holtz, E. G., Olivierre-Wilson, H., Ghosh, M. C., McConnell, J. P. and Rouault, T. A. (2005) Microcytic anemia, erythropoietic protoporphyria and neurodegeneration in mice with targeted deletion of iron regulatory protein 2. Blood 106, 1084-1091
195. Galy, B., Ferring, D., Minana, B., Bell, O., Janser, H. G., Muckenthaler, M., Schumann, K. and Hentze, M. W. (2005) Altered body iron distribution and microcytosis in mice deficient for iron regulatory protein 2 (IRP2). Blood 106, 2580-2589
196. Ferring-Appel, D., Hentze, M. W. and Galy, B. (2009) Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolism. Blood 113, 679-687
197. LaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S. K., Miller, G., Abu-Asab, M. and Tsokos, M. 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, 209-214
198. Ghosh, M. C., Ollivierre-Wilson, H., Cooperman, S. and Rouault, T. A. (2006) Reply to Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat. Genet. 38, 969-970
199. Smith, S. R., Cooperman, S., Lavaute, T., Tresser, N., Ghosh, M., Meyron-Holtz, E., Land, W., Ollivierre, H., Jortner, B. and Switzer, III, R. et al. (2004) Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Ann. N. Y. Acad. Sci. 1012, 65-83
200. Ghosh, M. C., Tong, W. H., Zhang, D., Ollivierre-Wilson, H., Singh, A., Krishna, M. C., Mitchell, J. B. and Rouault, T. A. (2008) Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice. Proc. Natl. Acad. Sci. U.S.A. 105, 12028-12033
201. Galy, B., Hölter, S. M., Klopstock, T., Ferring, D., Becker, L., Kaden, S., Wurst, W., Gröne, H.-J. and Hentze, M. W. (2006) Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat. Genet. 38, 967-969
202. Mueller, C., Magaki, S., Schrag, M., Ghosh, M. C. and Kirsch, W. M. (2009) Iron regulatory protein 2 is involved in brain copper homeostasis. J. Alzheimers Dis. 18, 201-210
203. Chen, G., Fillebeen, C., Wang, J. and Pantopoulos, K. (2007) Overexpression of iron regulatory protein 1 suppresses growth of tumor xenografts. Carcinogenesis 28, 785-791 (Pubitemid 46523335)
204. Maffettone, C., Chen, G., Drozdov, I., Ouzounis, C. and Pantopoulos, K. (2010) Tumorigenic properties of iron regulatory protein 2 (IRP2) mediated by its specific 73-amino acids insert. PLoS ONE 5, e10163
205. Wang, J. and Pantopoulos, K. (2002) Conditional de-repression of ferritin synthesis in cells expressing a constitutive IRP1 mutant. Mol. Cell. Biol. 22, 4638-4651
206. Wu, K. J., Polack, A. and Dalla-Favera, R. (1999) Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283, 676-679