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The many faces of the octahedral ferritin protein

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Abstract

Iron is an essential trace nutrient required for the active sites of many enzymes, electron transfer and oxygen transport proteins. In contrast, to its important biological roles, iron is a catalyst for reactive oxygen species (ROS). Organisms must acquire iron but must protect against oxidative damage. Biology has evolved siderophores, hormones, membrane transporters, and iron transport and storage proteins to acquire sufficient iron but maintain iron levels at safe concentrations that prevent iron from catalyzing the formation of ROS. Ferritin is an important hub for iron metabolism because it sequesters iron during times of iron excess and releases iron during iron paucity. Ferritin is expressed in response to oxidative stress and is secreted into the extracellular matrix and into the serum. The iron sequestering ability of ferritin is believed to be the source of the anti-oxidant properties of ferritin. In fact, ferritin has been used as a biomarker for disease because it is synthesized in response to oxidative damage and inflammation. The function of serum ferritin is poorly understood, however serum ferritin concentrations seem to correlate with total iron stores. Under certain conditions, ferritin is also associated with pro-oxidant activity. The source of this switch from anti-oxidant to pro-oxidant has not been established but may be associated with unregulated iron release from ferritin. Recent reports demonstrate that ferritin is involved in other aspects of biology such as cell activation, development, immunity and angiogenesis. This review examines ferritin expression and secretion in correlation with anti-oxidant activity and with respect to these new functions. In addition, conditions that lead to pro-oxidant conditions are considered.

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References

  • Alkhateeb AA, Connor JR (2010) Nuclear ferritin: a new role for ferritin in cell biology. Biochim Biophys Acta 1800(8):793–797

    PubMed  CAS  Google Scholar 

  • Andrews SC, Harrison PM, Guest JR (1989) Cloning, sequencing, and mapping of the bacterioferritin gene (bfr) of Escherichia coli K-12. J Bacteriol 171(7):3940–3947

    PubMed  CAS  Google Scholar 

  • Arosio P, Levi S (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 1800(8):783–792

    PubMed  CAS  Google Scholar 

  • Arosio P, Yokota M, Drysdale JW (1977) Characterization of serum ferritin in iron overload: possible identity to natural apoferritin. Br J Haematol 36(2):199–207

    Article  PubMed  CAS  Google Scholar 

  • Arosio P, Ingrassia R, Cavadini P (2009) Ferritins: a family of molecules for iron storage, antioxidation and more. Biochim Biophys Acta 1790(7):589–599. doi:10.1016/j.bbagen.2008.09.004

    PubMed  CAS  Google Scholar 

  • Aso Y, Takebayashi K, Wakabayashi S, Momobayashi A, Sugawara N, Terasawa T, Naruse R, Hara K, Suetsugu M, Morita K, Inukai T (2010) Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes. Diabetes Res Clin Pract 90(3):250–255. doi:10.1016/j.diabres.2010.09.008

    Google Scholar 

  • Azizova OA, Piryazev AP, Aseychev AV, Shvachko AG (2009a) Oxidative modification of fibrinogen inhibits its transformation into fibrin under the effect of thrombin. Bull Exp Biol Med 147(2):201–203

    Article  PubMed  CAS  Google Scholar 

  • Azizova OA, Shvachko AG, Aseichev AV (2009b) Effect of iron ions on functional activity of thrombin. Bull Exp Biol Med 148(5):776–779

    Article  PubMed  CAS  Google Scholar 

  • Beard JL, Murray-Kolb LE, Rosales FJ, Solomons NW, Angelilli ML (2006) Interpretation of serum ferritin concentrations as indicators of total-body iron stores in survey populations: the role of biomarkers for the acute phase response. Am J Clin Nutr 84(6):1498–1505

    PubMed  CAS  Google Scholar 

  • Bou-Abdallah F (2010) The iron redox and hydrolysis chemistry of the ferritins. Biochim Biophys Acta 1800(8):719–731

    PubMed  CAS  Google Scholar 

  • Cairo G, Tacchini L, Pogliaghi G, Anzon E, Tomasi A, Bernelli-Zazzera A (1995) Induction of ferritin synthesis by oxidative stress. Transcriptional and post-transcriptional regulation by expansion of the “free” iron pool. J Biol Chem 270(2):700–703

    Article  PubMed  CAS  Google Scholar 

  • Chakravarti S, Sabatos CA, Xiao S, Illes Z, Cha EK, Sobel RA, Zheng XX, Strom TB, Kuchroo VK (2005) Tim-2 regulates T helper type 2 responses and autoimmunity. J Exp Med 202(3):437–444. doi:10.1084/jem.20050308

    Article  PubMed  CAS  Google Scholar 

  • Chen TT, Li L, Chung D-H, Allen CDC, Torti SV, Torti FM, Cyster JG, Chen C-Y, 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(7):955–965. doi:10.1084/jem.20042433

    Article  PubMed  CAS  Google Scholar 

  • Chiancone E, Ceci P (2010) The multifaceted capacity of Dps proteins to combat bacterial stress conditions: detoxification of iron and hydrogen peroxide and DNA binding. Biochim Biophys Acta 1800(8):798–805

    PubMed  CAS  Google Scholar 

  • Coffman LG, Brown JC, Johnson DA, Parthasarathy N, D’Agostino RB Jr, Lively MO, Hua X, Tilley SL, Muller-Esterl W, Willingham MC, Torti FM, Torti SV (2008) Cleavage of high-molecular-weight kininogen by elastase and tryptase is inhibited by ferritin. Am J Physiol Lung Cell Mol Physiol 294(3):L505–L515. doi:10.1152/ajplung.00347.2007

    Article  PubMed  CAS  Google Scholar 

  • Colman RW (1994) Significance of the regulation of plasma kallikrein by alpha 2M. Ann N Y Acad Sci 737:347–367

    Article  PubMed  CAS  Google Scholar 

  • Cook JD, Lipschitz DA, Miles LE, Finch CA (1974) Serum ferritin as a measure of iron stores in normal subjects. Am J Clin Nutr 27(7):681–687

    PubMed  CAS  Google Scholar 

  • Crichton RR, Declercq J-P (2010) X-ray structures of ferritins and related proteins. Biochim Biophys Acta 1800(8):706–718

    PubMed  CAS  Google Scholar 

  • De Domenico I, Ward DM, Kaplan J (2009) Specific iron chelators determine the route of ferritin degradation. Blood 114(20):4546–4551. doi:10.1182/blood-2009-05-224188

    Article  PubMed  CAS  Google Scholar 

  • Depalma RG, Hayes VW, Chow BK, Shamayeva G, May PE, Zacharski LR (2010) Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. J Vasc Surg 51(6):1498–1503. doi:10.1016/j.jvs.2009.12.068

    Article  PubMed  Google Scholar 

  • Dickey LF, Sreedharan S, Theil EC, Didsbury JR, Wang YH, Kaufman RE (1987) Differences in the regulation of messenger RNA for housekeeping and specialized-cell ferritin. A comparison of three distinct ferritin complementary DNAs, the corresponding subunits, and identification of the first processed in amphibia. J Biol Chem 262(16):7901–7907

    PubMed  Google Scholar 

  • Fahmy M, Young SP (1993) Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA. Biochem J 296(Pt 1):175–181

    PubMed  CAS  Google Scholar 

  • Ganz T, Nemeth E (2009) Iron sequestration and anemia of inflammation. Semin Hematol 46(4):387–393. doi:10.1053/j.seminhematol.2009.06.001

    Article  PubMed  CAS  Google Scholar 

  • Garg RP, Vargo CJ, Cui X, Kurtz DM Jr (1996) A [2Fe-2S] protein encoded by an open reading frame upstream of the Escherichia coli bacterioferritin gene. Biochemistry 35(20):6297–6301. doi:10.1021/bi9600862

    Article  PubMed  CAS  Google Scholar 

  • Goessling LS, Mascotti DP, Bhattacharyya-Pakrasi M, Gang H, Thach RE (1994) Irreversible steps in the ferritin synthesis induction pathway. J Biol Chem 269(6):4343–4348

    PubMed  CAS  Google Scholar 

  • Goessling LS, Mascotti DP, Thach RE (1998) Involvement of heme in the degradation of iron-regulatory protein 2. J Biol Chem 273(20):12555–12557

    Article  PubMed  CAS  Google Scholar 

  • Gomez SL, Monteiro AM, Rabbani SR, Bloise AC, Carneiro SM, Alves S, Gidlund M, Abdalla DS, Neto AM (2010) Cu and Fe metallic ions-mediated oxidation of low-density lipoproteins studied by NMR, TEM and Z-scan technique. Chem Phys Lipids 163(6):545–551. doi:10.1016/j.chemphyslip.2010.03.008

    Article  PubMed  CAS  Google Scholar 

  • Hanson ES, Rawlins ML, Leibold EA (2003) Oxygen and iron regulation of iron regulatory protein 2. J Biol Chem 278(41):40337–40342. doi:10.1074/jbc.M302798200

    Article  PubMed  CAS  Google Scholar 

  • Herbert V, Jayatilleke E, Shaw S, Rosman AS, Giardina P, Grady RW, Bowman B, Gunter EW (1997) Serum ferritin iron, a new test, measures human body iron stores unconfounded by inflammation. Stem Cells 15(4):291–296

    Article  PubMed  CAS  Google Scholar 

  • Hintze KJ, Theil EC (2005) DNA and mRNA elements with complementary responses to hemin, antioxidant inducers, and iron control ferritin-L expression. Proc Natl Acad Sci USA 102(42):15048–15052. doi:10.1073/pnas.0505148102

    Article  PubMed  CAS  Google Scholar 

  • Hintze KJ, Theil EC (2006) Cellular regulation and molecular interactions of the ferritins. Cell Mol Life Sci 63(5):591–600. doi:10.1007/s00018-005-5285-y

    Article  PubMed  CAS  Google Scholar 

  • Hintze KJ, Katoh Y, Igarashi K, Theil EC (2007) Bach1 repression of ferritin and thioredoxin reductase1 is heme-sensitive in cells and in vitro and coordinates expression with heme oxygenase1, beta-globin, and NADP(H) quinone (oxido) reductase1. J Biol Chem 282(47):34365–34371. doi:10.1074/jbc.M700254200

    Article  PubMed  CAS  Google Scholar 

  • Ikegami Y, Inukai K, Imai K, Sakamoto Y, Katagiri H, Kurihara S, Awata T, Katayama S (2009) Adiponectin upregulates ferritin heavy chain in skeletal muscle cells. Diabetes 58(1):61–70. doi:10.2337/db07-0690

    Article  PubMed  CAS  Google Scholar 

  • Johnson J, Kenealey J, Hilton RJ, Brosnahan D, Watt RK, Watt GD (2011) Non-reductive iron release from horse spleen ferritin using desferoxamine chelation. J Inorg Biochem 105(2):202–207

    Article  PubMed  CAS  Google Scholar 

  • Kidane TZ, Sauble E, Linder MC (2006) Release of iron from ferritin requires lysosomal activity. Am J Physiol Cell Physiol 291(3):C445–C455. doi:10.1152/ajpcell.00505.2005

    Article  PubMed  CAS  Google Scholar 

  • Koorts AM, Viljoen M (2007) Ferritin and ferritin isoforms II: protection against uncontrolled cellular proliferation, oxidative damage and inflammatory processes. Arch Physiol Biochem 113(2):55–64

    Article  PubMed  CAS  Google Scholar 

  • Krause JR, Stolc V (1979) Serum ferritin and bone marrow iron stores I. Correlation with absence of iron in biopsy specimens. Am J Clin Pathol 72(5):817–820

    PubMed  CAS  Google Scholar 

  • Kruszewski M (2003) Labile iron pool: the main determinant of cellular response to oxidative stress. Mutat Res 531(1–2):81–92

    PubMed  CAS  Google Scholar 

  • Kurz T (2008) Can lipofuscin accumulation be prevented? Rejuvenation Res 11(2):441–443

    Article  PubMed  CAS  Google Scholar 

  • Kurz T, Terman A, Brunk UT (2007) Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron. Arch Biochem Biophys 462(2):220–230. doi:10.1016/j.abb.2007.01.013

    Article  PubMed  CAS  Google Scholar 

  • Lawson DM, Treffry A, Artymiuk PJ, Harrison PM, Yewdall SJ, Luzzago A, Cesareni G, Levi S, Arosio P (1989) Identification of the ferroxidase centre in ferritin. FEBS Lett 254(1–2):207–210

    Article  PubMed  CAS  Google Scholar 

  • Lawson DM, Artymiuk PJ, Yewdall SJ, Smith JM, Livingstone JC, Treffry A, Luzzago A, Levi S, Arosio P, Cesareni G et al (1991) Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature 349(6309):541–544. doi:10.1038/349541a0

    Article  PubMed  CAS  Google Scholar 

  • Lee DH, Jacobs DR Jr (2004) Serum markers of stored body iron are not appropriate markers of health effects of iron: a focus on serum ferritin. Med Hypotheses 62(3):442–445. doi:10.1016/S0306-9877(03)00344-X

    Article  PubMed  CAS  Google Scholar 

  • Leimberg MJ, Prus E, Konijn AM, Fibach E (2008) Macrophages function as a ferritin iron source for cultured human erythroid precursors. J Cell Biochem 103(4):1211–1218. doi:10.1002/jcb.21499

    Article  PubMed  CAS  Google Scholar 

  • 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(1):35–46. doi:10.1016/j.devcel.2008.12.002

    Article  PubMed  CAS  Google Scholar 

  • Li L, Fang CJ, Ryan JC, Niemi EC, Lebron JA, Bjorkman PJ, Arase H, Torti FM, Torti SV, Nakamura MC, Seaman WE (2010) Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc Natl Acad Sci USA 107(8):3505–3510. doi:10.1073/pnas.0913192107

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Jin W, Theil EC (2003) Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral. Proc Natl Acad Sci USA 100(7):3653–3658. doi:10.1073/pnas.0636928100

    Article  PubMed  CAS  Google Scholar 

  • Liu XS, Patterson LD, Miller MJ, Theil EC (2007) Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral. J Biol Chem 282(44):31821–31825. doi:10.1074/jbc.C700153200

    Article  PubMed  CAS  Google Scholar 

  • Madani N, Linder MC (1992) Differential effects of iron and inflammation on ferritin synthesis on free and membrane-bound polyribosomes of rat liver. Arch Biochem Biophys 299(2):206–213

    Article  PubMed  CAS  Google Scholar 

  • Moss D, Fargion S, Fracanzani AL, Levi S, Cappellini MD, Arosio P, Powell LW, Halliday JW (1992) Functional roles of the ferritin receptors of human liver, hepatoma, lymphoid and erythroid cells. J Inorg Biochem 47(3–4):219–227

    Article  PubMed  CAS  Google Scholar 

  • Nielsen P, Gunther U, Durken M, Fischer R, Dullmann J (2000) Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance. J Lab Clin Med 135(5):413–418. doi:10.1067/mlc.2000.106456

    Article  PubMed  CAS  Google Scholar 

  • Olson FJ, Sihlbom C, Davidsson P, Hulthe J, Fagerberg B, Bergstrom G (2010) Consistent differences in protein distribution along the longitudinal axis in symptomatic carotid atherosclerotic plaques. Biochem Biophys Res Commun 401(4):574–580. doi:10.1016/j.bbrc.2010.09.103

    Article  PubMed  CAS  Google Scholar 

  • Orino K, Yamamoto S, Watanabe K (1993) Fibrinogen as a ferritin-binding protein in horse plasma. J Vet Med Sci 55(5):785–787

    PubMed  CAS  Google Scholar 

  • Outten FW, Theil EC (2009) Iron-based redox switches in biology. Antioxid Redox Signal 11(5):1029–1046. doi:10.1089/ARS.2008.2296

    Article  PubMed  CAS  Google Scholar 

  • Pantopoulos K, Mueller S, Atzberger A, Ansorge W, Stremmel W, Hentze MW (1997) Differences in the regulation of iron regulatory protein-1 (IRP-1) by extra- and intracellular oxidative stress. J Biol Chem 272(15):9802–9808

    Article  PubMed  CAS  Google Scholar 

  • Parthasarathy N, Torti SV, Torti FM (2002) Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release. Biochem J 365(Pt 1):279–286

    Article  PubMed  CAS  Google Scholar 

  • Peslova G, Petrak J, Kuzelova K, Hrdy I, Halada P, Kuchel PW, Soe-Lin S, Ponka P, Sutak R, Becker E, Huang ML, Rahmanto YS, Richardson DR, Vyoral D (2009) Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood. Blood 113(24):6225–6236. doi:10.1182/blood-2009-01-201590

    Article  PubMed  CAS  Google Scholar 

  • Petersen CM (1993) Alpha 2-macroglobulin and pregnancy zone protein. Serum levels, alpha 2-macroglobulin receptors, cellular synthesis and aspects of function in relation to immunology. Dan Med Bull 40(4):409–446

    PubMed  CAS  Google Scholar 

  • Picard V, Epsztejn S, Santambrogio P, Cabantchik ZI, Beaumont C (1998) Role of ferritin in the control of the labile iron pool in murine erythroleukemia cells. J Biol Chem 273(25):15382–15386

    Article  PubMed  CAS  Google Scholar 

  • Ponka P, Beaumont C, Richardson DR (1998) Function and regulation of transferrin and ferritin. Semin Hematol 35(1):35–54

    PubMed  CAS  Google Scholar 

  • Qayyum R, Schulman P (2005) Iron and atherosclerosis. Clin Cardiol 28(3):119–122

    PubMed  Google Scholar 

  • Quail MA, Jordan P, Grogan JM, Butt JN, Lutz M, Thomson AJ, Andrews SC, Guest JR (1996) Spectroscopic and voltammetric characterisation of the bacterioferritin-associated ferredoxin of Escherichia coli. Biochem Biophys Res Commun 229(2):635–642

    Article  PubMed  CAS  Google Scholar 

  • Quintana C, Gutiérrez L (2010) Could a dysfunction of ferritin be a determinant factor in the aetiology of some neurodegenerative diseases? Biochim Biophys Acta 1800(8):770–782

    PubMed  CAS  Google Scholar 

  • Ramm GA, Britton RS, O’Neill R, Bacon BR (1994) Identification and characterization of a receptor for tissue ferritin on activated rat lipocytes. J Clin Invest 94(1):9–15. doi:10.1172/JCI117353

    Article  PubMed  CAS  Google Scholar 

  • Recalcati S, Invernizzi P, Arosio P, Cairo G (2008) New functions for an iron storage protein: the role of ferritin in immunity and autoimmunity. J Autoimmun 30(1–2):84–89. doi:10.1016/j.jaut.2007.11.003

    Article  PubMed  CAS  Google Scholar 

  • Regan RF, Li Z, Chen M, Zhang X, Chen-Roetling J (2008) Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide. Biochem Biophys Res Commun 375(1):6–10. doi:10.1016/j.bbrc.2008.07.061

    Article  PubMed  CAS  Google Scholar 

  • Romeo AM, Christen L, Niles EG, Kosman DJ (2001) Intracellular chelation of iron by bipyridyl inhibits DNA virus replication: ribonucleotide reductase maturation as a probe of intracellular iron pools. J Biol Chem 276(26):24301–24308. doi:10.1074/jbc.M010806200

    Article  PubMed  CAS  Google Scholar 

  • Rosenmund A, Haeberli A, Straub PW (1984) Blood coagulation and acute iron toxicity. Reversible iron-induced inactivation of serine proteases in vitro. J Lab Clin Med 103(4):524–533

    PubMed  CAS  Google Scholar 

  • Rouault TA, Tong WH (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6(4):345–351. doi:10.1038/nrm1620

    Article  PubMed  CAS  Google Scholar 

  • Sagastagoitia JD, Saez Y, Vacas M, Narvaez I, Saez de Lafuente JP, Molinero E, Magro A, Lafita M, Santos M, Escobar A, Iriarte JA (2007) Association between inflammation, lipid and hemostatic factors in patients with stable angina. Thromb Res 120(1):53–59. doi:10.1016/j.thromres.2006.06.013

    Article  PubMed  CAS  Google Scholar 

  • Sainz IM, Pixley RA, Colman RW (2007) Fifty years of research on the plasma kallikrein-kinin system: from protein structure and function to cell biology and in-vivo pathophysiology. Thromb Haemost 98(1):77–83

    PubMed  CAS  Google Scholar 

  • Sakamoto H, Kuboi T, Nagakura T, Hayashi S, Hoshi F, Mutoh K, Watanabe K, Orino K (2009) Characterization of feline serum ferritin-binding proteins: the presence of a novel ferritin-binding protein as an inhibitory factor in feline ferritin immunoassay. Biometals 22(5):793–802. doi:10.1007/s10534-009-9226-3

    Article  PubMed  CAS  Google Scholar 

  • Santambrogio P, Massover WH (1989) Rabbit serum alpha-2-macroglobulin binds to liver ferritin: association causes a heterogeneity of ferritin molecules. Br J Haematol 71(2):281–290

    Article  PubMed  CAS  Google Scholar 

  • Santambrogio P, Levi S, Cozzi A, Corsi B, Arosio P (1996) Evidence that the specificity of iron incorporation into homopolymers of human ferritin L- and H-chains is conferred by the nucleation and ferroxidase centres. Biochem J 314(Pt 1):139–144

    PubMed  CAS  Google Scholar 

  • Seki T, Kunichika T, Watanabe K, Orino K (2008) Apolipoprotein B binds ferritin by hemin-mediated binding: evidence of direct binding of apolipoprotein B and ferritin to hemin. Biometals 21(1):61–69

    Article  PubMed  CAS  Google Scholar 

  • Sharma JN (2005) The kallikrein-kinin system: from mediator of inflammation to modulator of cardioprotection. Inflammopharmacol 12(5–6):591–596. doi:10.1163/156856005774382760

    Article  CAS  Google Scholar 

  • Shcheglovitova ON, Azizova OA, Romanov YA, Aseichev AV, Litvina MM, Polosukhina ER, Mironchenkova EV (2006) Oxidized forms of fibrinogen induce expression of cell adhesion molecules by cultured endothelial cells from human blood vessels. Bull Exp Biol Med 142(3):308–312

    Article  PubMed  CAS  Google Scholar 

  • Shi H, Bencze KZ, Stemmler TL, Philpott CC (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320(5880):1207–1210. doi:10.1126/science.1157643

    Article  PubMed  CAS  Google Scholar 

  • Shull GE, Theil EC (1982) Translational control of ferritin synthesis by iron in embryonic reticulocytes of the bullfrog. J Biol Chem 257(23):14187–14191

    PubMed  CAS  Google Scholar 

  • 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(2):296–301

    Article  PubMed  CAS  Google Scholar 

  • Smirnov IM, Bailey K, Flowers CH, Garrigues NW, Wesselius LJ (1999) Effects of TNF-alpha and IL-1beta on iron metabolism by A549 cells and influence on cytotoxicity. Am J Physiol 277(2 Pt 1):L257–L263

    PubMed  CAS  Google Scholar 

  • Stassen JM, Arnout J, Deckmyn H (2004) The hemostatic system. Curr Med Chem 11(17):2245–2260

    PubMed  CAS  Google Scholar 

  • Steven Fishbane KK-ZARN (2004) Serum ferritin in chronic kidney disease: reconsidering the upper limit for iron treatment. Semin Dial 17(5):336–341

    Article  PubMed  Google Scholar 

  • Storey JA, Connor RF, Lewis ZT, Hurd D, Pomper G, Keung YK, Grover M, Lovato J, Torti SV, Torti FM, Molnar I (2009) The transplant iron score as a predictor of stem cell transplant survival. J Hematol Oncol 2:44. doi:10.1186/1756-8722-2-44

    Article  PubMed  CAS  Google Scholar 

  • Sugawara G, Inoue R, Watanabe K, Ohtsuka H, Orino K (2009) Short communication: bovine alpha-casein is a ferritin-binding protein and inhibitory factor of milk ferritin immunoassay. J Dairy Sci 92(8):3810–3814

    Article  PubMed  CAS  Google Scholar 

  • Syrovatka P, Kraml P, Potockova J, Fialova L, Vejrazka M, Crkovska J, Andel M (2009) Relationship between increased body iron stores, oxidative stress and insulin resistance in healthy men. Ann Nutr Metab 54(4):268–274. doi:10.1159/000229507

    Article  PubMed  CAS  Google Scholar 

  • Takagi H, Shi D, Ha Y, Allewell NM, Theil EC (1998) Localized unfolding at the junction of three ferritin subunits. A mechanism for iron release? J Biol Chem 273(30):18685–18688

    Article  PubMed  CAS  Google Scholar 

  • ten Kate J, Wolthuis A, Westerhuis B, van Deursen C (1997) The iron content of serum ferritin: physiological importance and diagnostic value. Eur J Clin Chem Clin Biochem 35(1):53–56

    PubMed  CAS  Google Scholar 

  • Theil EC (2007) Coordinating responses to iron and oxygen stress with DNA and mRNA promoters: the ferritin story. Biometals 20(3–4):513–521. doi:10.1007/s10534-006-9063-6

    Article  PubMed  CAS  Google Scholar 

  • Theil EC, Liu XS, Tosha T (2008) Gated pores in the ferritin protein nanocage. Inorganica Chim Acta 361(4):868–874. doi:10.1016/j.ica.2007.08.025

    Article  PubMed  CAS  Google Scholar 

  • Todorich B, Zhang X, Slagle-Webb B, Seaman WE, Connor JR (2008) Tim-2 is the receptor for H-ferritin on oligodendrocytes. J Neurochem 107(6):1495–1505. doi:10.1111/j.1471-4159.2008.05678.x

    Article  PubMed  CAS  Google Scholar 

  • Torti SV, Torti FM (1994) Iron and ferritin in inflammation and cancer. Adv Inorg Biochem 10:119–137

    PubMed  CAS  Google Scholar 

  • Torti FM, Torti SV (2002) Regulation of ferritin genes and protein. Blood 99(10):3505–3516

    Article  PubMed  CAS  Google Scholar 

  • Torti SV, Kwak EL, Miller SC, Miller LL, Ringold GM, Myambo KB, Young AP, Torti FM (1988) The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene. J Biol Chem 263(25):12638–12644

    PubMed  CAS  Google Scholar 

  • Tran TN, Eubanks SK, Schaffer KJ, Zhou CYJ, Linder MC (1997) Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood 90(12):4979–4986

    PubMed  CAS  Google Scholar 

  • Wallander ML, Leibold EA, Eisenstein RS (2006) Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim Biophys Acta 1763(7):668–689

    Article  PubMed  CAS  Google Scholar 

  • Wang A, Zeng Y, Han H, Weeratunga S, Morgan BN, Moenne-Loccoz P, Schonbrunn E, Rivera M (2007) Biochemical and structural characterization of Pseudomonas aeruginosa Bfd and FPR: ferredoxin NADP+ reductase and not ferredoxin is the redox partner of heme oxygenase under iron-starvation conditions. Biochemistry 46(43):12198–12211. doi:10.1021/bi7013135

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV (2010) Serum ferritin: past, present and future. Biochim Biophys Acta 1800(8):760–769. doi:10.1016/j.bbagen.2010.03.011

    PubMed  CAS  Google Scholar 

  • Watt RK, Hilton RJ, Graff DM (2010) Oxido-reduction is not the only mechanism allowing ions to traverse the ferritin protein shell. Biochim Biophys Acta 1800(8):745–759

    PubMed  CAS  Google Scholar 

  • Weeratunga SK, Gee CE, Lovell S, Zeng Y, Woodin CL, Rivera M (2009) Binding of Pseudomonas aeruginosa apobacterioferritin-associated ferredoxin to bacterioferritin B promotes heme mediation of electron delivery and mobilization of core mineral iron. Biochemistry 48(31):7420–7431. doi:10.1021/bi900561a

    Article  PubMed  CAS  Google Scholar 

  • Wei Y, Miller SC, Tsuji Y, Torti SV, Torti FM (1990) Interleukin 1 induces ferritin heavy chain in human muscle cells. Biochem Biophys Res Commun 169(1):289–296

    Article  PubMed  CAS  Google Scholar 

  • Worwood M, Dawkins S, Wagstaff M, Jacobs A (1976) The purification and properties of ferritin from human serum. Biochem J 157(1):97–103

    PubMed  CAS  Google Scholar 

  • Yamanishi H, Iyama S, Yamaguchi Y, Kanakura Y, Iwatani Y (2002) Relation between iron content of serum ferritin and clinical status factors extracted by factor analysis in patients with hyperferritinemia. Clin Biochem 35(7):523–529

    Article  PubMed  CAS  Google Scholar 

  • Yuan XM, Li W, Baird SK, Carlsson M, Melefors O (2004) Secretion of ferritin by iron-laden macrophages and influence of lipoproteins. Free Radic Res 38(10):1133–1142. doi:10.1080/10715760400011692

    Article  PubMed  CAS  Google Scholar 

  • Zahringer J, Baliga BS, Munro HN (1976) Novel mechanism for translational control in regulation of ferritin synthesis by iron. Proc Natl Acad Sci USA 73(3):857–861

    Article  PubMed  CAS  Google Scholar 

  • Zumbrennen KB, Wallander ML, Romney SJ, Leibold EA (2009) Cysteine oxidation regulates the RNA-binding activity of iron regulatory protein 2. Mol Cell Biol 29(8):2219–2229. doi:10.1128/MCB.00004-09

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Robert J. Hilton for assistance with preparing figures and proofreading of the manuscript.

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  1. Department of Chemistry and Biochemistry, Brigham Young University, C-210 BNSN Building, Provo, UT, 84604, USA

    Richard K. Watt

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Correspondence to Richard K. Watt.

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Watt, R.K. The many faces of the octahedral ferritin protein. Biometals 24, 489–500 (2011). https://doi.org/10.1007/s10534-011-9415-8

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  • DOI: https://doi.org/10.1007/s10534-011-9415-8

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