Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

Archives of Toxicology

Volumn 88, Issue 10, 2014, Pages 1787-1802

  Finazzi, Dario ^a,b   Arosio, Paolo ^a  

^a UNIVERSITY OF BRESCIA   (Italy)

^b SPEDALI CIVILI   (Italy)

Author keywords

Ferritin; Iron; Neurodegeneration; Oxidative stress

Indexed keywords

FERRITIN; IRON; REACTIVE OXYGEN METABOLITE;

ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; COMPLICATION; CYTOSOL; GENE EXPRESSION REGULATION; GENETICS; HEMOCHROMATOSIS; HUMAN; METABOLISM; MITOCHONDRION; MUTATION; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS;

ANIMALS; CYTOSOL; FERRITINS; GENE EXPRESSION REGULATION; HEMOCHROMATOSIS; HUMANS; IRON; MITOCHONDRIA; MODELS, MOLECULAR; MUTATION; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 84922233989     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-014-1329-0     Document Type: Review

References (163)

1. An SH, Kang JH (2013) Oxidative damage of DNA induced by the reaction of methylglyoxal with lysine in the presence of ferritin. BMB Rep 46:225–229
2. Andrews SC (2010) The Ferritin-like superfamily: evolution of the biological iron storeman from a rubrerythrin-like ancestor. Biochim Biophys Acta 1800:691–705. doi:10.1016/j.bbagen.2010.05.010
3. Arosio P, Levi S (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 1800:783–792. doi:10.1016/j.bbagen.2010.02.005
4. Asano T, Komatsu M, Yamaguchi-Iwai Y et al (2011) Distinct mechanisms of ferritin delivery to lysosomes in iron-depleted and iron-replete cells. Mol Cell Biol 31:2040–2052. doi:10.1128/MCB.01437-10
5. Baraibar MA, Barbeito AG, Muhoberac BB, Vidal R (2008) Iron-mediated aggregation and a localized structural change characterize ferritin from a mutant light chain polypeptide that causes neurodegeneration. J Biol Chem 283:31679–31689. doi:10.1074/jbc.M805532200
6. Barbeito AG, Garringer HJ, Baraibar MA et al (2009) Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene. J Neurochem 109:1067–1078. doi:10.1111/j.1471-4159.2009.06028.x
7. Bartnikas TB, Campagna DR, Antiochos B et al (2010) Characterization of mitochondrial ferritin-deficient mice. Am J Hematol 85:958–960. doi:10.1002/ajh.21872
8. Bartzokis G, Cummings JL, Markham CH et al (1999) MRI evaluation of brain iron in earlier- and later-onset Parkinson’s disease and normal subjects. Magn Reson Imaging 17:213–222
9. Beaumont C, Leneuve P, Devaux I et al (1995) Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nat Genet 11:444–446. doi:10.1038/ng1295-444
10. Becerril-Ortega J, Bordji K, Fréret T et al (2014) Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer’s disease. Neurobiol Aging 35:2288–2301. doi:10.1016/j.neurobiolaging.2014.04.019
11. Bou-Abdallah F (2010) The iron redox and hydrolysis chemistry of the ferritins. Biochim Biophys Acta 1800:719–731. doi:10.1016/j.bbagen.2010.03.021
12. Bou-Abdallah F, Papaefthymiou GC, Scheswohl DM et al (2002) mu-1,2-Peroxobridged di-iron(III) dimer formation in human H-chain ferritin. Biochem J 364:57–63
13. Bou-Abdallah F, Santambrogio P, Levi S et al (2005) Unique iron binding and oxidation properties of human mitochondrial ferritin: a comparative analysis with Human H-chain ferritin. J Mol Biol 347:543–554. doi:10.1016/j.jmb.2005.01.007
14. Bulvik BE, Berenshtein E, Meyron-Holtz EG et al (2012) Cardiac protection by preconditioning is generated via an iron-signal created by proteasomal degradation of iron proteins. PLoS One 7:e48947. doi:10.1371/journal.pone.0048947
15. Cairo G, Bardella L, Schiaffonati L et al (1985) Multiple mechanisms of iron-induced ferritin synthesis in HeLa cells. Biochem Biophys Res Commun 133:314–321
16. Campanella A, Rovelli E, Santambrogio P et al (2009) Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia. Hum Mol Genet 18:1–11. doi:10.1093/hmg/ddn308
17. Cazzola M, Arosio P, Bellotti V et al (1985) Immunological reactivity of serum ferritin in patients with malignancy. Tumori 71:547–554
18. Cazzola M, Invernizzi R, Bergamaschi G et al (2003) Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood 101:1996–2000. doi:10.1182/blood-2002-07-2006
19. Chasteen ND (1998) Ferritin. Uptake, storage, and release of iron. Met Ions Biol Syst 35:479–514
20. Chasteen ND, Harrison PM (1999) Mineralization in ferritin: an efficient means of iron storage. J Struct Biol 126:182–194. doi:10.1006/jsbi.1999.4118
21. Chevion M, Leibowitz S, Aye NN et al (2008) Heart protection by ischemic preconditioning: a novel pathway initiated by iron and mediated by ferritin. J Mol Cell Cardiol 45:839–845. doi:10.1016/j.yjmcc.2008.08.011
22. Cocco E, Porrini V, Derosas M et al (2013) Protective effect of mitochondrial ferritin on cytosolic iron dysregulation induced by doxorubicin in HeLa cells. Mol Biol Rep 40:6757–6764. doi:10.1007/s11033-013-2792-z
23. Cojoc M, Peitzsch C, Trautmann F et al (2013) Emerging targets in cancer management: role of the CXCL12/CXCR4 axis. Onco Targets Ther 6:1347–1361. doi:10.2147/OTT.S36109
24. Connor JR, Boeshore KL, Benkovic SA, Menzies SL (1994) Isoforms of ferritin have a specific cellular distribution in the brain. J Neurosci Res 37:461–465. doi:10.1002/jnr.490370405
25. Connor JR, Snyder BS, Arosio P et al (1995) A quantitative analysis of isoferritins in select regions of aged, Parkinsonian, and Alzheimer’s diseased brains. J Neurochem 65:717–724
26. Connor JR, Boyer PJ, Menzies SL et al (2003) Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology 61:304–309
27. Corsi B, Cozzi A, Arosio P et al (2002) Human mitochondrial ferritin expressed in HeLa cells incorporates iron and affects cellular iron metabolism. J Biol Chem 277:22430–22437. doi:10.1074/jbc.M105372200
28. Cowley JM, Janney DE, Gerkin RC, Buseck PR (2000) The structure of ferritin cores determined by electron nanodiffraction. J Struct Biol 131:210–216. doi:10.1006/jsbi.2000.4292
29. Cozzi A, Corsi B, Levi S et al (2000) Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity. J Biol Chem 275:25122–25129. doi:10.1074/jbc.M003797200
30. Cozzi A, Levi S, Corsi B et al (2003) Role of iron and ferritin in TNFalpha-induced apoptosis in HeLa cells. FEBS Lett 537:187–192
31. Cozzi A, Santambrogio P, Corsi B et al (2006) Characterization of the l-ferritin variant 460InsA responsible of a hereditary ferritinopathy disorder. Neurobiol Dis 23:644–652. doi:10.1016/j.nbd.2006.05.004
32. Cozzi A, Rovelli E, Frizzale G et al (2010) Oxidative stress and cell death in cells expressing L-ferritin variants causing neuroferritinopathy. Neurobiol Dis 37:77–85. doi:10.1016/j.nbd.2009.09.009
33. Cozzi A, Santambrogio P, Privitera D et al (2013) Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome. J Exp Med 210:1779–1791. doi:10.1084/jem.20130315
34. Cremonesi L, Cozzi A, Girelli D et al (2004) Case report: a subject with a mutation in the ATG start codon of L-ferritin has no haematological or neurological symptoms. J Med Genet 41:e81
35. Crompton DE, Chinnery PF, Fey C et al (2002) Neuroferritinopathy: a window on the role of iron in neurodegeneration. Blood Cells Mol Dis 29:522–531
36. Darshan D, Vanoaica L, Richman L et al (2009) Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage. Hepatology 50:852–860. doi:10.1002/hep.23058
37. De Domenico I, Vaughn MB, Li L et al (2006) Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J 25:5396–5404. doi:10.1038/sj.emboj.7601409
38. De Domenico I, Ward DM, Kaplan J (2009) Specific iron chelators determine the route of ferritin degradation. Blood 114:4546–4551. doi:10.1182/blood-2009-05-224188
39. Della Porta MG, Malcovati L, Invernizzi R et al (2006) Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome. Leukemia 20:549–555. doi:10.1038/sj.leu.2404142
40. Devos D, Moreau C, Devedjian JC et al (2014) Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal 21:195–210. doi:10.1089/ars.2013.5593
41. Dexter DT, Wells FR, Lees AJ et al (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52:1830–1836
42. Dexter DT, Carayon A, Vidailhet M et al (1990) Decreased ferritin levels in brain in Parkinson’s disease. J Neurochem 55:16–20
43. Drysdale JW, Adelman TG, Arosio P et al (1977) Human isoferritins in normal and disease states. Semin Hematol 14:71–88
44. Drysdale J, Arosio P, Invernizzi R et al (2002) Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol Dis 29:376–383
45. Duce JA, Tsatsanis A, Cater MA et al (2010) Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer’s disease. Cell 142:857–867. doi:10.1016/j.cell.2010.08.014
46. Earley CJ, Barker PB, Horská A, Allen RP (2006) MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome. Sleep Med 7:458–461. doi:10.1016/j.sleep.2005.11.009
47. Epsztejn S, Glickstein H, Picard V et al (1999) H-ferritin subunit overexpression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood 94:3593–3603
48. Faucheux BA, Martin M-E, Beaumont C et al (2002) Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson’s disease. J Neurochem 83:320–330
49. Ferraro S, Mozzi R, Panteghini M (2012) Revaluating serum ferritin as a marker of body iron stores in the traceability era. Clin Chem Lab Med 50:1911–1916. doi:10.1515/cclm-2012-0129
50. Ferreira C, Bucchini D, Martin ME et al (2000) Early embryonic lethality of H ferritin gene deletion in mice. J Biol Chem 275:3021–3024
51. Frey AG, Nandal A, Park JH et al (2014) Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase. Proc Natl Acad Sci USA 111:8031–8036. doi:10.1073/pnas.1402732111
52. Galazka-Friedman J, Bauminger ER, Koziorowski D, Friedman A (2004) Mössbauer spectroscopy and ELISA studies reveal differences between Parkinson’s disease and control substantia nigra. Biochim Biophys Acta 1688:130–136. doi:10.1016/j.bbadis.2003.11.005
53. Gálvez N, Fernández B, Sánchez P et al (2008) Comparative structural and chemical studies of ferritin cores with gradual removal of their iron contents. J Am Chem Soc 130:8062–8068. doi:10.1021/ja800492z
54. Garner B, Roberg K, Brunk UT (1998) Endogenous ferritin protects cells with iron-laden lysosomes against oxidative stress. Free Radic Res 29:103–114
55. Goralska M, Holley BL, McGahan MC (2001) Overexpression of H- and L-ferritin subunits in lens epithelial cells: Fe metabolism and cellular response to UVB irradiation. Invest Ophthalmol Vis Sci 42:1721–1727
56. Gozzelino R, Andrade BB, Larsen R et al (2012) Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host Microbe 12:693–704. doi:10.1016/j.chom.2012.10.011
57. Guo B, Phillips JD, Yu Y, Leibold EA (1995) Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem 270:21645–21651
58. Hailemariam K, Iwasaki K, Huang B-W et al (2010) Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress. J Cell Sci 123:3863–3871. doi:10.1242/jcs.073627
59. Hanson ES, Rawlins ML, Leibold EA (2003) Oxygen and iron regulation of iron regulatory protein 2. J Biol Chem 278:40337–40342. doi:10.1074/jbc.M302798200
60. Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275:161–203
61. Hentze MW, Rouault TA, Harford JB, Klausner RD (1989) Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction. Science 244:357–359
62. Hevi S, Chuck SL (2003) Ferritins can regulate the secretion of apolipoprotein B. J Biol Chem 278:31924–31929. doi:10.1074/jbc.M303081200
63. 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 102:15048–15052. doi:10.1073/pnas.0505148102
64. Hintze KJ, Theil EC (2006) Cellular regulation and molecular interactions of the ferritins. Cell Mol Life Sci 63:591–600. doi:10.1007/s00018-005-5285-y
65. 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 282:34365–34371. doi:10.1074/jbc.M700254200
66. Ikegami Y, Inukai K, Imai K et al (2009) Adiponectin upregulates ferritin heavy chain in skeletal muscle cells. Diabetes 58:61–70. doi:10.2337/db07-0690
67. Iwasaki K, Mackenzie EL, Hailemariam K et al (2006) Hemin-mediated regulation of an antioxidant-responsive element of the human ferritin H gene and role of Ref-1 during erythroid differentiation of K562 cells. Mol Cell Biol 26:2845–2856. doi:10.1128/MCB.26.7.2845-2856.2006
68. Iwasaki K, Hailemariam K, Tsuji Y (2007) PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element. J Biol Chem 282:22335–22343. doi:10.1074/jbc.M701477200
69. Iwasaki K, Ray PD, Huang B-W et al (2013) Role of AMP-activated protein kinase in ferritin H gene expression by resveratrol in human T cells. Biochemistry 52:5075–5083. doi:10.1021/bi400399f
70. Johnson JL, Norcross DC, Arosio P et al (1999) Redox reactivity of animal apoferritins and apoheteropolymers assembled from recombinant heavy and light human chain ferritins. Biochemistry 38:4089–4096. doi:10.1021/bi982690d
71. Jones T, Spencer R, Walsh C (1978) Mechanism and kinetics of iron release from ferritin by dihydroflavins and dihydroflavin analogues. Biochemistry 17:4011–4017
72. Kang JH (2009) Ferritin enhances salsolinol-mediated DNA strand breakage: protection by carnosine and related compounds. Toxicol Lett 188:20–25. doi:10.1016/j.toxlet.2009.02.011
73. Kannengiesser C, Jouanolle A-M, Hetet G et al (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 94:335–339. doi:10.3324/haematol.2008.000125
74. Kaur D, Yantiri F, Rajagopalan S 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
75. Kaur D, Rajagopalan S, Andersen JK (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. doi:10.1016/j.brainres.2009.08.043
76. Kidane TZ, Sauble E, Linder MC (2006) Release of iron from ferritin requires lysosomal activity. Am J Physiol Cell Physiol 291:C445–C455. doi:10.1152/ajpcell.00505.2005
77. Koziorowski D, Friedman A, Arosio P et al (2007) ELISA reveals a difference in the structure of substantia nigra ferritin in Parkinson’s disease and incidental Lewy body compared to control. Parkinsonism Relat Disord 13:214–218. doi:10.1016/j.parkreldis.2006.10.002
78. Langlois d’Estaintot B, Santambrogio P, Granier T et al (2004) Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. J Mol Biol 340:277–293. doi:10.1016/j.jmb.2004.04.036
79. Larson JA, Howie HL, So M (2004) Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source. Mol Microbiol 53:807–820. doi:10.1111/j.1365-2958.2004.04169.x
80. Leidgens S, Bullough KZ, Shi H et al (2013) Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin. J Biol Chem 288:17791–17802. doi:10.1074/jbc.M113.460253
81. Levi S, Arosio P (2004) Mitochondrial ferritin. Int J Biochem Cell Biol 36:1887–1889. doi:10.1016/j.biocel.2003.10.020
82. Levi S, Finazzi D (2014) Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms. Front Pharmacol 5:99. doi:10.3389/fphar.2014.00099
83. Levi S, Corsi B, Bosisio M et al (2001) A human mitochondrial ferritin encoded by an intronless gene. J Biol Chem 276:24437–24440. doi:10.1074/jbc.C100141200
84. Li R, Luo C, Mines M et al (2006) Chemokine CXCL12 induces binding of ferritin heavy chain to the chemokine receptor CXCR4, alters CXCR4 signaling, and induces phosphorylation and nuclear translocation of ferritin heavy chain. J Biol Chem 281:37616–37627. doi:10.1074/jbc.M607266200
85. Li X, Liu Y, Zheng Q et al (2013) Ferritin light chain interacts with PEN-2 and affects γ-secretase activity. Neurosci Lett 548:90–94. doi:10.1016/j.neulet.2013.05.018
86. Licker V, Turck N, Kövari E et al (2014) Proteomic analysis of human substantia nigra identifies novel candidates involved in Parkinson’s disease pathogenesis. Proteomics 14:784–794. doi:10.1002/pmic.201300342
87. Linder MC (2013) Mobilization of stored iron in mammals: a review. Nutrients 5:4022–4050. doi:10.3390/nu5104022
88. Liu Y, Hu N (2009) Electrochemical detection of natural DNA damage induced by ferritin/ascorbic acid/H2O2 system and amplification of DNA damage by endonuclease Fpg. Biosens Bioelectron 25:185–190. doi:10.1016/j.bios.2009.06.035
89. Liu X, Theil EC (2005) Ferritins: dynamic management of biological iron and oxygen chemistry. Acc Chem Res 38:167–175. doi:10.1021/ar0302336
90. 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 282:31821–31825. doi:10.1074/jbc.C700153200
91. Lovell MA, Robertson JD, Teesdale WJ et al (1998) Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158:47–52
92. Maccarinelli F, Gammella E, Asperti M et al (2014) Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity. J Mol Med (Berl). doi:10.1007/s00109-014-1147-0
93. MacKenzie EL, Ray PD, Tsuji Y (2008) Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress. Free Radic Biol Med 44:1762–1771. doi:10.1016/j.freeradbiomed.2008.01.031
94. Mancias JD, Wang X, Gygi SP et al (2014) Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509:105–109. doi:10.1038/nature13148
95. Mancone C, Montaldo C, Santangelo L et al (2012) Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection. J Proteome Res 11:2786–2797. doi:10.1021/pr201128s
96. Martsev SP, Vlasov AP, Arosio P (1998) Distinct stability of recombinant L and H subunits of human ferritin: calorimetric and ANS binding studies. Protein Eng 11:377–381
97. McNeill A, Chinnery PF (2012) Neuroferritinopathy: update on clinical features and pathogenesis. Curr Drug Targets 13:1200–1203
98. Nandal A, Ruiz JC, Subramanian P et al (2011) Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2. Cell Metab 14:647–657. doi:10.1016/j.cmet.2011.08.015
99. Nie G, Sheftel AD, Kim SF, Ponka P (2005) Overexpression of mitochondrial ferritin causes cytosolic iron depletion and changes cellular iron homeostasis. Blood 105:2161–2167. doi:10.1182/blood-2004-07-2722
100. Oakley AE, Collingwood JF, Dobson J et al (2007) Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology 68:1820–1825. doi:10.1212/01.wnl.0000262033.01945.9a
101. Obolensky A, Berenshtein E, Konijn AM et al (2008) Ischemic preconditioning of the rat retina: protective role of ferritin. Free Radic Biol Med 44:1286–1294. doi:10.1016/j.freeradbiomed.2007.10.060
102. Pantopoulos K, Mueller S, Atzberger A et al (1997) Differences in the regulation of iron regulatory protein-1 (IRP-1) by extra- and intracellular oxidative stress. J Biol Chem 272:9802–9808
103. Pennell DJ, Carpenter JP, Roughton M, Cabantchik Z (2011) On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure. J Cardiovasc Magn Reson 13:45. doi:10.1186/1532-429X-13-45
104. Pham CG, Bubici C, Zazzeroni F et al (2004) Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119:529–542. doi:10.1016/j.cell.2004.10.017
105. Pitcher J, Abt A, Myers J, Han R, Snyder M, Graziano A, Festa L, Kutzler M, Garcia F, Gao WJ, Fischer-Smith T, Rappaport J, Meucci O (2014) Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction. J Clin Invest 124(2):656–669. doi:10.1172/JCI70090
106. Prusiner SB (1998) The prion diseases. Brain Pathol 8:499–513
107. Prusiner SB (2013) Biology and genetics of prions causing neurodegeneration. Annu Rev Genet 47:601–623. doi:10.1146/annurev-genet-110711-155524
108. Punta M, Coggill PC, Eberhardt RY et al (2012) The Pfam protein families database. Nucleic Acids Res 40:D290–D301. doi:10.1093/nar/gkr1065
109. Quintana C, Gutiérrez L (2010) Could a dysfunction of ferritin be a determinant factor in the aetiology of some neurodegenerative diseases? Biochim Biophys Acta 1800:770–782. doi:10.1016/j.bbagen.2010.04.012
110. Rashid KA, Hevi S, Chen Y et al (2002) A proteomic approach identifies proteins in hepatocytes that bind nascent apolipoprotein B. J Biol Chem 277:22010–22017. doi:10.1074/jbc.M112448200
111. Richards TD, Pitts KR, Watt GD (1996) A kinetic study of iron release from Azotobacter vinelandii bacterial ferritin. J Inorg Biochem 61:1–13
112. Roberts BR, Ryan TM, Bush AI et al (2012) The role of metallobiology and amyloid-β peptides in Alzheimer’s disease. J Neurochem 120(Suppl 1):149–166. doi:10.1111/j.1471-4159.2011.07500.x
113. Rogers JT, Randall JD, Cahill CM et al (2002) An iron-responsive element type II in the 5′-untranslated region of the Alzheimer’s amyloid precursor protein transcript. J Biol Chem 277:45518–45528. doi:10.1074/jbc.M207435200
114. Rouault TA, Tong W-H (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6:345–351. doi:10.1038/nrm1620
115. Rudeck M, Volk T, Sitte N, Grune T (2000) Ferritin oxidation in vitro: implication of iron release and degradation by the 20S proteasome. IUBMB Life 49:451–456. doi:10.1080/152165400410317
116. Sakamoto K, Iwasaki K, Sugiyama H, Tsuji Y (2009) Role of the tumor suppressor PTEN in antioxidant responsive element-mediated transcription and associated histone modifications. Mol Biol Cell 20:1606–1617. doi:10.1091/mbc.E08-07-0762
117. Santambrogio P, Cozzi A, Levi S, Arosio P (1987) Human serum ferritin G-peptide is recognized by anti-L ferritin subunit antibodies and concanavalin-A. Br J Haematol 65:235–237
118. Santambrogio P, Levi S, Cozzi A et al (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
119. Santambrogio P, Biasiotto G, Sanvito F et al (2007) Mitochondrial ferritin expression in adult mouse tissues. J Histochem Cytochem 55:1129–1137. doi:10.1369/jhc.7A7273.2007
120. Schmidauer C, Sojer M, Seppi K et al (2005) Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome. Ann Neurol 58:630–634. doi:10.1002/ana.20572
121. Sengupta R, Burbassi S, Shimizu S et al (2009) Morphine increases brain levels of ferritin heavy chain leading to inhibition of CXCR4-mediated survival signaling in neurons. J Neurosci 29:2534–2544. doi:10.1523/JNEUROSCI.5865-08.2009
122. Shi H, Bencze KZ, Stemmler TL, Philpott CC (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320:1207–1210. doi:10.1126/science.1157643
123. Shi Z-H, Nie G, Duan X-L et al (2010) Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine-induced dopaminergic cell damage: implication for neuroprotection in Parkinson’s disease. Antioxid Redox Signal 13:783–796. doi:10.1089/ars.2009.3018
124. Singh A, Isaac AO, Luo X et al (2009a) Abnormal brain iron homeostasis in human and animal prion disorders. PLoS Pathog 5:e1000336. doi:10.1371/journal.ppat.1000336
125. Singh A, Kong Q, Luo X et al (2009b) Prion protein (PrP) knock-out mice show altered iron metabolism: a functional role for PrP in iron uptake and transport. PLoS One 4:e6115. doi:10.1371/journal.pone.0006115
126. Singh A, Qing L, Kong Q, Singh N (2012) Change in the characteristics of ferritin induces iron imbalance in prion disease affected brains. Neurobiol Dis 45:930–938. doi:10.1016/j.nbd.2011.12.012
127. Singh A, Haldar S, Horback K et al (2013) Prion protein regulates iron transport by functioning as a ferrireductase. J Alzheimers Dis 35:541–552. doi:10.3233/JAD-130218
128. Singh N, Haldar S, Tripathi AK et al (2014) Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid Redox Signal 20:1324–1363. doi:10.1089/ars.2012.4931
129. Snyder AM, Connor JR (2009) Iron, the substantia nigra and related neurological disorders. Biochim Biophys Acta 1790:606–614. doi:10.1016/j.bbagen.2008.08.005
130. Snyder AM, Wang X, Patton SM et al (2009) Mitochondrial ferritin in the substantia nigra in restless legs syndrome. J Neuropathol Exp Neurol 68:1193–1199. doi:10.1097/NEN.0b013e3181bdc44f
131. Sofic E, Riederer P, Heinsen H et al (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74:199–205
132. Sultana R, Boyd-Kimball D, Cai J et al (2007) Proteomics analysis of the Alzheimer’s disease hippocampal proteome. J Alzheimers Dis 11:153–164
133. Takahashi T, Kuyucak S (2003) Functional properties of threefold and fourfold channels in ferritin deduced from electrostatic calculations. Biophys J 84:2256–2263. doi:10.1016/S0006-3495(03)75031-0
134. Theil EC (2007) Coordinating responses to iron and oxygen stress with DNA and mRNA promoters: the ferritin story. Biometals 20:513–521. doi:10.1007/s10534-006-9063-6
135. Theil EC (2013) Ferritin: the protein nanocage and iron biomineral in health and in disease. Inorg Chem 52:12223–12233. doi:10.1021/ic400484n
136. Theil EC, Liu XS, Tosha T (2008) Gated pores in the ferritin protein nanocage. Inorganica Chim Acta 361:868–874. doi:10.1016/j.ica.2007.08.025
137. Thompson K, Menzies S, Muckenthaler M et al (2003) Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress. J Neurosci Res 71:46–63. doi:10.1002/jnr.10463
138. Torti FM, Torti SV (2002) Regulation of ferritin genes and protein. Blood 99:3505–3516
139. Truty J, Malpe R, Linder MC (2001) Iron prevents ferritin turnover in hepatic cells. J Biol Chem 276:48775–48780. doi:10.1074/jbc.M105392200
140. Vanoaica L, Darshan D, Richman L et al (2010) Intestinal ferritin H is required for an accurate control of iron absorption. Cell Metab 12:273–282. doi:10.1016/j.cmet.2010.08.003
141. Vanoaica L, Richman L, Jaworski M et al (2014) Conditional deletion of ferritin h in mice reduces B and T lymphocyte populations. PLoS One 9:e89270. doi:10.1371/journal.pone.0089270
142. Vercellotti GM, Khan FB, Nguyen J et al (2014) H-ferritin ferroxidase induces cytoprotective pathways and inhibits microvascular stasis in transgenic sickle mice. Front Pharmacol 5:79. doi:10.3389/fphar.2014.00079
143. Vidal R, Miravalle L, Gao X et al (2008) Expression of a mutant form of the ferritin light chain gene induces neurodegeneration and iron overload in transgenic mice. J Neurosci 28:60–67. doi:10.1523/JNEUROSCI.3962-07.2008
144. Wagstaff M, Worwood M, Jacobs A (1978) Properties of human tissue isoferritins. Biochem J 173:969–977
145. Wang PJ, McCarrey JR, Yang F, Page DC (2001) An abundance of X-linked genes expressed in spermatogonia. Nat Genet 27:422–426. doi:10.1038/86927
146. Wang W, Knovich MA, Coffman LG et al (2010) Serum ferritin: past, present and future. Biochim Biophys Acta 1800:760–769. doi:10.1016/j.bbagen.2010.03.011
147. Wang L, Yang H, Zhao S et al (2011) Expression and localization of mitochondrial ferritin mRNA in Alzheimer’s disease cerebral cortex. PLoS One 6:e22325. doi:10.1371/journal.pone.0022325
148. Wardeska JG, Viglione B, Chasteen ND (1986) Metal ion complexes of apoferritin. Evidence for initial binding in the hydrophilic channels. J Biol Chem 261:6677–6683
149. Watt GD, Jacobs D, Frankel RB (1988) Redox reactivity of bacterial and mammalian ferritin: is reductant entry into the ferritin interior a necessary step for iron release? Proc Natl Acad Sci USA 85:7457–7461
150. Weiss A, Brill B, Borghouts C et al (2012) Survivin inhibition by an interacting recombinant peptide, derived from the human ferritin heavy chain, impedes tumor cell growth. J Cancer Res Clin Oncol 138:1205–1220. doi:10.1007/s00432-012-1195-1
151. Wu W-S, Zhao Y-S, Shi Z-H et al (2013) Mitochondrial ferritin attenuates β-amyloid-induced neurotoxicity: reduction in oxidative damage through the Erk/P38 mitogen-activated protein kinase pathways. Antioxid Redox Signal 18:158–169. doi:10.1089/ars.2011.4285
152. Wypijewska A, Galazka-Friedman J, Bauminger ER et al (2010) Iron and reactive oxygen species activity in parkinsonian substantia nigra. Parkinsonism Relat Disord 16:329–333. doi:10.1016/j.parkreldis.2010.02.007
153. Yanatori I, Yasui Y, Tabuchi M, Kishi F (2014) Chaperone protein involved in transmembrane transport of iron. Biochem J. doi:10.1042/BJ20140225
154. Yang X, Arosio P, Chasteen ND (2000) Molecular diffusion into ferritin: pathways, temperature dependence, incubation time, and concentration effects. Biophys J 78:2049–2059. doi:10.1016/S0006-3495(00)76752-X
155. Yang X, Cohen MV, Downey JM (2010) Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc Drugs Ther 24:225–234. doi:10.1007/s10557-010-6236-x
156. Yuan X, Cong Y, Hao J et al (2004) Regulation of LIP level and ROS formation through interaction of H-ferritin with G-CSF receptor. J Mol Biol 339:131–144. doi:10.1016/j.jmb.2004.03.027
157. Zarjou A, Bolisetty S, Joseph R et al (2013) Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury. J Clin Invest 123:4423–4434. doi:10.1172/JCI67867
158. Zecca L, Youdim MBH, Riederer P et al (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5:863–873. doi:10.1038/nrn1537
159. Zecca L, Berg D, Arzberger T et al (2005) In vivo detection of iron and neuromelanin by transcranial sonography: a new approach for early detection of substantia nigra damage. Mov Disord 20:1278–1285. doi:10.1002/mds.20550
160. Zhang Y, Mikhael M, Xu D et al (2010) Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit. Antioxid Redox Signal 13:999–1009. doi:10.1089/ars.2010.3129
161. Zhao G, Bou-Abdallah F, Arosio P et al (2003) Multiple pathways for mineral core formation in mammalian apoferritin. The role of hydrogen peroxide. Biochemistry 42:3142–3150. doi:10.1021/bi027357v
162. Zieger MAJ, Gupta MP (2009) Hypothermic preconditioning of endothelial cells attenuates cold-induced injury by a ferritin-dependent process. Free Radic Biol Med 46:680–691. doi:10.1016/j.freeradbiomed.2008.12.004
163. Zumbrennen KB, Wallander ML, Romney SJ, Leibold EA (2009) Cysteine oxidation regulates the RNA-binding activity of iron regulatory protein 2. Mol Cell Biol 29:2219–2229. doi:10.1128/MCB.00004-09