Journal of Neural Transmission

, Volume 118, Issue 3, pp 337–347 | Cite as

A possible role for secreted ferritin in tissue iron distribution

  • Esther G. Meyron-HoltzEmail author
  • Shirly Moshe-Belizowski
  • Lyora A. Cohen
Basic Neurosciences, Genetics and Immunology - Review Article


Ferritin is known as a well-conserved iron detoxification and storage protein that is found in the cytosol of many prokaryotic and eukaryotic organisms. In insects and worms, ferritin has evolved into a classically secreted protein that transports iron systemically. Mammalian ferritins are found intracellularly in the cytosol, as well as in the nucleus, the endo-lysosomal compartment and the mitochondria. Extracellular ferritin is found in fluids such as serum and synovial and cerebrospinal fluids. We recently characterized the biophysical properties, secretion mechanism and cellular origin of mouse serum ferritin, which is actively secreted by a non-classical pathway involving lysosomal processing. Here, we review the data to support a hypothesis that intracellular and extracellular ferritin may play a role in intra- and intercellular redistribution of iron.


Extracellular ferritin Iron trafficking Serum ferritin Secretory lysosome 



We thank the organizers of the symposium on “Iron in Brain Function and Neurodegenerative Disorders” in honor of Moussa Youdim’s 70th birthday, S. Mandel, P. Riederer and E. Gruenblatt for putting together an outstanding program that inspired us to write this contribution. Our thanks are also due to Fanis Missirlis and Marianna Truman for critical reading, and to the US–Israel Binational Science Foundation, Grant #2007466 to Esther Meyron-Holtz and Tracey Rouault for financial support.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abboud S, Haile DJ (2000) A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 275(26):19906–19912PubMedCrossRefGoogle Scholar
  2. Abe E, Arai M (1992) Synovial fluid ferritin in traumatic hemarthrosis, rheumatoid arthritis and osteoarthritis. Tohoku J Exp Med 168(3):499–505PubMedCrossRefGoogle Scholar
  3. Alkhateeb AA, Connor JR (2010) Nuclear ferritin: a new role for ferritin in cell biology. Biochim Biophys Acta 1800(8):793–797PubMedGoogle Scholar
  4. Almeida SM, Cunha DS, Yamada E, Doi EM, Ono M (2008) Quantification of cerebrospinal fluid ferritin as a biomarker for CNS malignant infiltration. Arquivos de neuro-psiquiatria 66(3B):720–724PubMedGoogle Scholar
  5. Andrews NC (2008) Forging a field: the golden age of iron biology. Blood 112(2):219–230PubMedCrossRefGoogle Scholar
  6. Arosio P, Yokota M, Drysdale JW (1977) Characterization of serum ferritin in iron overload: possible identity to natural apoferritin. Br J Haematol 36(2):199–207PubMedCrossRefGoogle Scholar
  7. Arosio P, Levi S, Santambrogio P, Cozzi A, Luzzago A, Cesareni G, Albertini A (1991) Structural and functional studies of human ferritin H and L chains. Curr Stud Hematol Blood Transfus 58:127–131Google Scholar
  8. Arosio P, Ingrassia R, Cavadini P (2009) Ferritins: a family of molecules for iron storage, antioxidation and more. Biochim Biophys Acta 1790(7):589–599PubMedGoogle Scholar
  9. Bao G, Clifton M, Hoette TM, Mori K, Deng SX, Qiu A, Viltard M, Williams D, Paragas N, Leete T, Kulkarni R, Li X, Lee B, Kalandadze A, Ratner AJ, Pizarro JC, Schmidt-Ott KM, Landry DW, Raymond KN, Strong RK, Barasch J (2010) Iron traffics in circulation bound to a siderocalin (Ngal)–catechol complex. Nat Chem Biol 6(8):602–609PubMedCrossRefGoogle Scholar
  10. Baraibar MA, Muhoberac BB, Garringer HJ, Hurley TD, Vidal R (2010) Unraveling of the E-helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration. J Biol Chem 285(3):1950–1956PubMedCrossRefGoogle Scholar
  11. Barbarese E, Koppel DE, Deutscher MP, Smith CL, Ainger K, Morgan F, Carson JH (1995) Protein translation components are colocalized in granules in oligodendrocytes. J Cell Sci 108(Pt 8):2781–2790PubMedGoogle Scholar
  12. Blake DR, Bacon PA, Eastham EJ, Brigham K (1980) Synovial fluid ferritin in rheumatoid arthritis. Br Med J 281(6242):715–716PubMedCrossRefGoogle Scholar
  13. Blott EJ, Griffiths GM (2002) Secretory lysosomes. Nat Rev 3(2):122–131CrossRefGoogle Scholar
  14. Bridges KR (1987) Ascorbic acid inhibits lysosomal autophagy of ferritin. J Biol Chem 262(30):14773–14778PubMedGoogle Scholar
  15. Cadenas E (1989) Biochemistry of oxygen toxicity. Annu Rev Biochem 58:79–110PubMedCrossRefGoogle Scholar
  16. Cairo G, Rappocciolo E, Tacchini L, Schiaffonati L (1991) Expression of the genes for the ferritin H and L subunits in rat liver and heart, evidence for tissue-specific regulations at pre- and post-translational levels. Biochem J 275(Pt 3):813–816PubMedGoogle Scholar
  17. Carroll G, Sharma G, Upadhyay A, Jazayeri J (2010) Ferritin concentrations in synovial fluid are higher in osteoarthritis patients with HFE gene mutations (C282Y or H63D). Scand J Rheumatol 39(5):413–420Google Scholar
  18. Cassanelli S, Moulis J (2001) Sulfide is an efficient iron releasing agent for mammalian ferritins. Biochim Biophys Acta 1547(1):174–182PubMedCrossRefGoogle Scholar
  19. 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(7):955–965PubMedCrossRefGoogle Scholar
  20. Chinta SJ, Andersen JK (2005) Dopaminergic neurons. Int J Biochem Cell Biol 37(5):942–946PubMedCrossRefGoogle Scholar
  21. Clardy SL, Earley CJ, Allen RP, Beard JL, Connor JR (2006) Ferritin subunits in CSF are decreased in restless legs syndrome. J Lab Clin Med 147(2):67–73PubMedCrossRefGoogle Scholar
  22. Coffman LG, Parsonage D, D’Agostino R Jr, Torti FM, Torti SV (2009) Regulatory effects of ferritin on angiogenesis. Proc Natl Acad Sci USA 106(2):570–575PubMedCrossRefGoogle Scholar
  23. Cohen LA, Gutierrez L, Weiss A, Leichtmann-Bardoogo Y, Zhang DL, Crooks DR, Sougrat R, Morgenstern A, Galy B, Hentze MW, Lazaro FJ, Rouault TA, Meyron-Holtz EG (2010) Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 116(9):1574–1584PubMedCrossRefGoogle Scholar
  24. Cozzi A, Rovelli E, Frizzale G, Campanella A, Amendola M, Arosio P, Levi S (2010) Oxidative stress and cell death in cells expressing L-ferritin variants causing neuroferritinopathy. Neurobiol Dis 37(1):77–85PubMedCrossRefGoogle Scholar
  25. Curtis AR, Fey C, Morris CM, Bindoff LA, Ince PG, Chinnery PF, Coulthard A, Jackson MJ, Jackson AP, McHale DP, Hay D, Barker WA, Markham AF, Bates D, Curtis A, Burn J (2001) Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet 28(4):350–354PubMedCrossRefGoogle Scholar
  26. De Domenico I, Vaughn MB, Li L, Bagley D, Musci G, Ward DM, Kaplan J (2006) Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J 25(22):5396–5404PubMedCrossRefGoogle Scholar
  27. Devireddy LR, Hart DO, Goetz DH, Green MR (2010) A mammalian siderophore synthesized by an enzyme with a bacterial homolog involved in enterobactin production. Cell 141(6):1006–1017PubMedCrossRefGoogle Scholar
  28. Dong XP, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H (2008) The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 455(7215):992–996PubMedCrossRefGoogle Scholar
  29. 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) Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403(6771):776–781PubMedCrossRefGoogle Scholar
  30. Dunkov B, Georgieva T (2006) Insect iron binding proteins: insights from the genomes. Insect Biochem Mol Biol 36(4):300–309PubMedCrossRefGoogle Scholar
  31. Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP (2000) Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 54(8):1698–1700PubMedGoogle Scholar
  32. Ferring-Appel D, Hentze MW, Galy B (2009) Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolism. Blood 113(3):679–687PubMedCrossRefGoogle Scholar
  33. Flanagan PR, Lam D, Banerjee D, Valberg LS (1989) Ferritin release by mononuclear cells in hereditary hemochromatosis. J Lab Clin Med 113(2):145–150PubMedGoogle Scholar
  34. Friedman A, Galazka-Friedman J, Koziorowski D (2009) Iron as a cause of Parkinson disease: a myth or a well established hypothesis? Parkinsonism Relat Disord 15(Suppl 3):S212–S214PubMedCrossRefGoogle Scholar
  35. Fukunaga M, Li TQ, van Gelderen P, de Zwart JA, Shmueli K, Yao B, Lee J, Maric D, Aronova MA, Zhang G, Leapman RD, Schenck JF, Merkle H, Duyn JH (2010) Layer-specific variation of iron content in cerebral cortex as a source of MRI contrast. Proc Natl Acad Sci USA 107(8):3834–3839PubMedCrossRefGoogle Scholar
  36. Galazka-Friedman J, Bauminger ER, Koziorowski D, Friedman A (2004) Mossbauer spectroscopy and ELISA studies reveal differences between Parkinson’s disease and control substantia nigra. Biochim Biophys Acta 1688(2):130–136PubMedGoogle Scholar
  37. Galvez N, Fernandez B, Sanchez P, Cuesta R, Ceolin M, Clemente-Leon M, Trasobares S, Lopez-Haro M, Calvino JJ, Stephan O, Dominguez-Vera JM (2008) Comparative structural and chemical studies of ferritin cores with gradual removal of their iron contents. J Am Chem Soc 130(25):8062–8068PubMedCrossRefGoogle Scholar
  38. Greco TM, Seeholzer SH, Mak A, Spruce L, Ischiropoulos H (2010) Quantitative mass spectrometry-based proteomics reveals the dynamic range of primary mouse astrocyte protein secretion. J Proteome Res 9(5):2764–2774PubMedCrossRefGoogle Scholar
  39. Gruenheid S, Cellier M, Vidal S, Gros P (1995) Identification and characterization of a second mouse Nramp gene. Genomics 25(2):514–525PubMedCrossRefGoogle Scholar
  40. 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(6641):482–488PubMedCrossRefGoogle Scholar
  41. Hallgren B, Sourander P (1958) The effect of age on the non-haemin iron in the human brain. J Neurochem 3(1):41–51PubMedCrossRefGoogle Scholar
  42. Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275(3):161–203PubMedCrossRefGoogle Scholar
  43. Hasan MR, Morishima D, Tomita K, Katsuki M, Kotani S (2005) Identification of a 250 kDa putative microtubule-associated protein as bovine ferritin. Evidence for a ferritin–microtubule interaction. FEBS J 272(3):822–831PubMedCrossRefGoogle Scholar
  44. Hasan MR, Koikawa S, Kotani S, Miyamoto S, Nakagawa H (2006) Ferritin forms dynamic oligomers to associate with microtubules in vivo: implication for the role of microtubules in iron metabolism. Exp Cell Res 312(11):1950–1960PubMedCrossRefGoogle Scholar
  45. Hulet SW, Hess EJ, Debinski W, Arosio P, Bruce K, Powers S, Connor JR (1999) Characterization and distribution of ferritin binding sites in the adult mouse brain. J Neurochem 72(2):868–874PubMedCrossRefGoogle Scholar
  46. Iancu TC, Neustein HB, Landing BH (1976) The liver in thalassaemia major: ultrastructural observations. Ciba Found Symp 51:293–316Google Scholar
  47. Infante AA, Infante D, Chan MC, How PC, Kutschera W, Linhartova I, Mullner EW, Wiche G, Propst F (2007) Ferritin associates with marginal band microtubules. Exp Cell Res 313(8):1602–1614PubMedCrossRefGoogle Scholar
  48. Jacobs A (1984) Serum ferritin and malignant tumours. Med Oncol Tumor Pharmacother 1(3):149–156PubMedGoogle Scholar
  49. Kakuta K, Orino K, Yamamoto S, Watanabe K (1997) High levels of ferritin and its iron in fetal bovine serum. Comp Biochem Physiol A Physiol 118(1):165–169PubMedCrossRefGoogle Scholar
  50. Kannengiesser C, Jouanolle AM, Hetet G, Mosser A, Muzeau F, Henry D, Bardou-Jacquet E, Mornet M, Brissot P, Deugnier Y, Grandchamp B, Beaumont C (2009) A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload. Haematologica 94(3):335–339PubMedCrossRefGoogle Scholar
  51. Knowles RB, Sabry JH, Martone ME, Deerinck TJ, Ellisman MH, Bassell GJ, Kosik KS (1996) Translocation of RNA granules in living neurons. J Neurosci 16(24):7812–7820PubMedGoogle Scholar
  52. Kong P, Wang L, Zhang H, Zhou Z, Qiu L, Gai Y, Song L (2010) Two novel secreted ferritins involved in immune defense of Chinese mitten crab Eriocheir sinensis. Fish Shellfish Immunol 28(4):604–612PubMedCrossRefGoogle Scholar
  53. Konijn AM, Meyron-Holtz EG, Levy R, Ben-Bassat H, Matzner Y (1990) Specific binding of placental acidic isoferritin to cells of the T-cell line HD-MAR. FEBS Lett 263(2):229–232PubMedCrossRefGoogle Scholar
  54. Koziorowski D, Friedman A, Arosio P, Santambrogio P, Dziewulska D (2007) ELISA reveals a difference in the structure of substantia nigra ferritin in Parkinson’s disease and incidental Lewy body compared to control. Parkinson Relat Disord 13(4):214–218CrossRefGoogle Scholar
  55. Kuiper MA, Mulder C, van Kamp GJ, Scheltens P, Wolters EC (1994) Cerebrospinal fluid ferritin levels of patients with Parkinson’s disease, Alzheimer’s disease, and multiple system atrophy. J Neural Trans 7(2):109–114CrossRefGoogle Scholar
  56. Lambotte O, Cacoub P, Costedoat N, Le Moel G, Amoura Z, Piette JC (2003) High ferritin and low glycosylated ferritin may also be a marker of excessive macrophage activation. J Rheumatol 30(5):1027–1028PubMedGoogle Scholar
  57. Leimberg JM, Konijn AM, Fibach E (2005) Macrophages promote development of human erythroid precursors in transferrin-free culture medium. Hematology 10(1):73–76PubMedCrossRefGoogle Scholar
  58. 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):1211–1218PubMedCrossRefGoogle Scholar
  59. Levi S, Arosio P (2004) Mitochondrial ferritin. Int J Biochem Cell Biol 36(10):1887–1889PubMedCrossRefGoogle Scholar
  60. Levi S, Luzzago A, Cesareni G, Cozzi A, Franceschinelli F, Albertini A, Arosio P (1988) Mechanism of ferritin iron uptake: activity of the H-chain and deletion mapping of the ferro-oxidase site. A study of iron uptake and ferro-oxidase activity of human liver, recombinant H-chain ferritins, and of two H-chain deletion mutants. J Biol Chem 263(34):18086–18092PubMedGoogle Scholar
  61. LeVine SM, Macklin WB (1990) Iron-enriched oligodendrocytes: a reexamination of their spatial distribution. J Neurosci Res 26(4):508–512PubMedCrossRefGoogle Scholar
  62. 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. Develop Cell 16(1):35–46CrossRefGoogle Scholar
  63. 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):3505–3510PubMedCrossRefGoogle Scholar
  64. 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(37):13612–13617PubMedCrossRefGoogle Scholar
  65. Luscieti S, Santambrogio P, Langlois d’Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P (2010) Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem 285(16):11948–11957PubMedCrossRefGoogle Scholar
  66. Matzner Y, Konijn AM, Hershko C (1980) Serum ferritin in hematologic malignancies. Am J Hematol 9(1):13–22PubMedCrossRefGoogle Scholar
  67. 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(2):299–309PubMedCrossRefGoogle Scholar
  68. 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 (New York, NY) 291(5509):1755–1759CrossRefGoogle Scholar
  69. Mikhael M, Sheftel AD, Ponka P (2010) Ferritin does not donate its iron for haem synthesis in macrophages. Biochem J 429(3):463–471PubMedCrossRefGoogle Scholar
  70. Missirlis F, Kosmidis S, Brody T, Mavrakis M, Holmberg S, Odenwald WF, Skoulakis EM, Rouault TA (2007) Homeostatic mechanisms for iron storage revealed by genetic manipulations and live imaging of Drosophila ferritin. Genetics 177(1):89–100PubMedCrossRefGoogle Scholar
  71. Montalto E, Mangraviti S, Costa G, Carrega P, Morandi B, Pezzino G, Bonaccorsi I, Cancellieri A, Mingari MC, Mesiti M, Ferlazzo G, Melioli G (2010) Seroma fluid subsequent to axillary lymph node dissection for breast cancer derives from an accumulation of afferent lymph. Immunol Lett 131(1):67–72PubMedCrossRefGoogle Scholar
  72. Morris CM, Candy JM, Oakley AE, Bloxham CA, Edwardson JA (1992) Histochemical distribution of non-haem iron in the human brain. Acta Anat 144(3):235–257PubMedCrossRefGoogle Scholar
  73. Moss D, Powell LW, Arosio P, Halliday JW (1992) Characterization of the ferritin receptors of human T lymphoid (MOLT-4) cells. J Lab Clin Med 119(3):273–279PubMedGoogle Scholar
  74. Nagatsu T (1995) Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. Essays Biochem 30:15–35PubMedGoogle Scholar
  75. Nichol H, Law JH, Winzerling JJ (2002) Iron metabolism in insects. Annu Rev Entomol 47:535–559PubMedCrossRefGoogle Scholar
  76. O’Keeffe ST, Gavin K, Lavan JN (1994) Iron status and restless legs syndrome in the elderly. Age Ageing 23(3):200–203PubMedCrossRefGoogle Scholar
  77. 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(11):1264–1269PubMedCrossRefGoogle Scholar
  78. Ota T, Katsuki I (1998) Ferritin subunits in sera and synovial fluids from patients with rheumatoid arthritis. J Rheumatol 25(12):2315–2318PubMedGoogle Scholar
  79. Outten FW, Theil EC (2009) Iron-based redox switches in biology. Antioxid Redox Signal 11(5):1029–1046PubMedCrossRefGoogle Scholar
  80. Parry DH, Worwood M, Jacobs A (1975) Serum ferritin in acute leukaemia at presentation and during remission. Br Med J 1(5952):245–247PubMedCrossRefGoogle Scholar
  81. Pierrel F, Cobine PA, Winge DR (2007) Metal ion availability in mitochondria. Biometals 20(3–4):675–682PubMedCrossRefGoogle Scholar
  82. Pollack MS, da Silva BM, Moshief RD, Groshen S, Bognacki J, Dupont B, de Sousa M (1983) Ferritin secretion by human mononuclear cells: association with HLA phenotype. Clin Immunol Immunopathol 27(1):124–134PubMedCrossRefGoogle Scholar
  83. Radisky DC, Kaplan J (1998) Iron in cytosolic ferritin can be recycled through lysosomal degradation in human fibroblasts. Biochem J 336(1):201–205PubMedGoogle Scholar
  84. Ramm GA, Powell LW, Halliday JW (1994) Pathways of intracellular trafficking and release of ferritin by the liver in vivo: the effect of chloroquine and cytochalasin D. Hepatology (Baltimore, MD) 19(2):504–513Google Scholar
  85. 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):84–89PubMedCrossRefGoogle Scholar
  86. Ringeling PL, Cleton MI, Kroos MJ, Sorber LW, de Bruyn WC, Harrison PM, van Eijk HG (1989) Lysosomal and cytosolic ferritins. A biochemical and electron-spectroscopic study. Biol Met 2(2):114–121PubMedCrossRefGoogle Scholar
  87. Rouault TA (2001) Iron on the brain. Nat Genet 28(4):299–300PubMedCrossRefGoogle Scholar
  88. Sammarco MC, Ditch S, Banerjee A, Grabczyk E (2008) Ferritin L and H subunits are differentially regulated on a post-transcriptional level. J Biol Chem 283(8):4578–4587PubMedCrossRefGoogle Scholar
  89. Schenck JF, Zimmerman EA (2004) High-field magnetic resonance imaging of brain iron: birth of a biomarker? NMR Biomed 17(7):433–445PubMedCrossRefGoogle Scholar
  90. Schonberg DL, McTigue DM (2009) Iron is essential for oligodendrocyte genesis following intraspinal macrophage activation. Exp Neurol 218(1):64–74PubMedCrossRefGoogle Scholar
  91. 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(7080):96–100PubMedCrossRefGoogle Scholar
  92. Shi H, Bencze KZ, Stemmler TL, Philpott CC (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science (New York, NY) 320(5880):1207–1210CrossRefGoogle Scholar
  93. 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 (Baltimore, MD) 8(2):296–301Google Scholar
  94. Sindic CJ, Collet-Cassart D, Cambiaso CL, Masson PL, Laterre EC (1981) The clinical relevance of ferritin concentration in the cerebrospinal fluid. J Neurol Neurosurg Psychiatry 44(4):329–333PubMedCrossRefGoogle Scholar
  95. Stam TC, Swaak AJ, Kruit WH, Eggermont AM (2002) Regulation of ferritin: a specific role for interferon-alpha (IFN-alpha)? The acute phase response in patients treated with IFN-alpha-2b. Eur J Clin Invest 32(Suppl 1):79–83PubMedCrossRefGoogle Scholar
  96. Steward O (1997) mRNA localization in neurons: a multipurpose mechanism? Neuron 18(1):9–12PubMedCrossRefGoogle Scholar
  97. Stinchcombe J, Bossi G, Griffiths GM (2004) Linking albinism and immunity: the secrets of secretory lysosomes. Science (New York, NY) 305(5680):55–59CrossRefGoogle Scholar
  98. Szymendera JJ, Kozlowicz-Gudzinska I, Madej G, Sikorowa L, Kaminska JA, Kowalska M (1985) Clinical usefulness of serum ferritin measurements in patients with testicular germ cell tumors. Oncology 42(4):253–258PubMedCrossRefGoogle Scholar
  99. Theil EC, Matzapetakis M, Liu X (2006) Ferritins: iron/oxygen biominerals in protein nanocages. J Biol Inorg Chem 11(7):803–810PubMedCrossRefGoogle Scholar
  100. Torti SV, Torti FM (1998) Human H-kininogen is a ferritin-binding protein. J Biol Chem 273(22):13630–13635PubMedCrossRefGoogle Scholar
  101. Tran TN, Eubanks SK, Schaffer KJ, Zhou CY, Linder MC (1997) Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood 90(12):4979–4986PubMedGoogle Scholar
  102. Vaisman B, Fibach E, Konijn AM (1997) Utilization of intracellular ferritin iron for hemoglobin synthesis in developing human erythroid precursors. Blood 90(2):831–838PubMedGoogle Scholar
  103. van der Sluijs P, Neeft M, van Vlijmen T, Elstak E, Wieffer M (2008) Methods for analysis of rab27a/Munc13-4 in secretory lysosome release in hematopoietic cells. Methods Enzymol 438:185–201PubMedCrossRefGoogle Scholar
  104. Vanoaica L, Darshan D, Richman L, Schumann K, Kuhn LC (2010) Intestinal ferritin H is required for an accurate control of iron absorption. Cell Metabol 12(3):273–282CrossRefGoogle Scholar
  105. Vidal S, Gros P, Skamene E (1995) Natural resistance to infection with intracellular parasites: molecular genetics identifies Nramp1 as the Bcg/Ity/Lsh locus. J Leukoc Biol 58(4):382–390PubMedGoogle Scholar
  106. Watanabe K, Muranishi N, Murata Y, Orino K, Okano S, Yamamoto S (2000) Biochemical properties of canine serum ferritin: iron content and nonbinding to concanavalin A. Biometals 13(4):319–324PubMedCrossRefGoogle Scholar
  107. Worwood M (1979) Serum ferritin. CRC Crit Rev Clin Lab Sci 10(2):171–204PubMedCrossRefGoogle Scholar
  108. Worwood M, Cragg SJ, Wagstaff M, Jacobs A (1979) Binding of human serum ferritin to concanavalin A. Clin Sci (Lond) 56(1):83–87Google Scholar
  109. 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):1133–1142PubMedCrossRefGoogle Scholar
  110. Zandman-Goddard G, Matzner Y, Konijn AM, Hershko C (1986) Cerebrospinal fluid ferritin in malignant CNS involvement. Cancer 58(6):1346–1349PubMedCrossRefGoogle Scholar
  111. Zhang DL, Su D, Berczi A, Vargas A, Asard H (2006a) An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes. Biochim Biophys Acta 1760(12):1903–1913PubMedGoogle Scholar
  112. Zhang X, Surguladze N, Slagle-Webb B, Cozzi A, Connor JR (2006b) Cellular iron status influences the functional relationship between microglia and oligodendrocytes. Glia 54(8):795–804PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Esther G. Meyron-Holtz
    • 1
    Email author
  • Shirly Moshe-Belizowski
    • 1
  • Lyora A. Cohen
    • 1
  1. 1.Laboratory for Molecular Nutrition, Faculty of Biotechnology and Food Engineering, TechnionTechnion City, HaifaIsrael

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