Intracellular Iron Transport and Storage: From Molecular Mechanisms to Health Implications

In the paper

“Likewise, an excess of iron systemically and at the cellular level leads to deleterious effects including free radical-induced damage to cells, cellular components, tissues, and organs.”

In the paper

“Deviations from normal iron levels have been indicated in the pathogenesis of aging, neurodegenerative disease, cancer, and infection (18, 23, 156, 180, 299, 334).”

What the sources say

• Not checked yetcites [18] Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003;133:1468S–1472S. doi: 10.1093/jn/133.5.1468S. [DOI] [PubMed] [Google Scholar] source
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In the paper

“excess “labile iron” is potentially detrimental to the cell or organism or both because of its propensity to participate in oxidation–reduction reactions that generate harmful free radicals”

• Also stated in: § I. Introduction · plain

  “This propensity to undergo oxidation-reduction reactions is also responsible for the toxicity of iron (229).”

What the sources say

• Not checked yetcites [229] Papanikolaou G. Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharmacol. 2005;202:199–211. doi: 10.1016/j.taap.2004.06.021. [DOI] [PubMed] [Google Scholar] source

In the paper

“Iron binding and release are coordinated by a conformational change in which the two subdomains of each lobe open, and the N1, N2, C1, and C2 domains twist (114, 115).”

What the sources say

• Not checked yetcites [114] Grossmann JG. Neu M. Evans RW. Lindley PF. Appel H. Hasnain SS. Metal-induced conformational changes in transferrins. J Mol Biol. 1993;229:585–590. doi: 10.1006/jmbi.1993.1063. [DOI] [PubMed] [Google Scholar] source
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In the paper

“In nonintestinal cells, circulating iron is bound to transferrin (Tf) and is imported via receptor-mediated endocytosis after binding to the transferrin receptor (TfR) (249).”

What the sources say

• Not checked yetcites [249] Ponka P. Beaumont C. Richardson DR. Function and regulation of transferrin and ferritin. Semin Hematol. 1998;35:35–54. [PubMed] [Google Scholar] source

In the paper

“Only 1 to 2 mg of iron comes from intestinal iron sources; thus, other mechanisms for iron regulation, including release of iron from cellular storage depots and recycling of iron from protein sources, are critically important to provide for organismal iron requirements.”

In the paper

“Tf is also involved in the transport of iron from reticuloendocytic cells [red blood cell (RBC) recycling] and the liver to proliferative cells throughout the body, thereby controlling the levels of “labile iron” (293).”

What the sources say

• Not checked yetcites [293] Thorstensen K. Romslo I. The role of transferrin in the mechanism of cellular iron uptake. Biochem J. 1990;271:1–9. doi: 10.1042/bj2710001. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Because Tf and TfR are absent from enterocytes, Tf binds iron and plays an essential role in the transport of iron only once it is exported from duodenal enterocytes into the bloodstream.”

In the paper

“The promoter of TfR1 contains a hypoxia-responsive element (HRE) within a 100-bp sequence located upstream of the transcription start site (190).”

What the sources say

• Not checked yetcites [190] Lok CN. Ponka P. Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem. 1999;274:24147–24152. doi: 10.1074/jbc.274.34.24147. [DOI] [PubMed] [Google Scholar] source

In the paper

“Both IRP1 and IRP2 are activated by iron-deficient conditions, leading them to bind the target IREs (130).”

What the sources say

• Not checked yetcites [130] Hentze MW. Kuhn LC. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci U S A. 1996;93:8175–8182. doi: 10.1073/pnas.93.16.8175. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Tf bound with iron releases iron at acidic pH because of major conformational changes including a 54- to 63-degree rotation between the two domains on each lobe (103).”

What the sources say

• Not checked yetcites [103] Gerstein M. Anderson BF. Norris GE. Baker EN. Lesk AM. Chothia C. Domain closure in lactoferrin: two hinges produce a see-saw motion between alternative close-packed interfaces. J Mol Biol. 1993;234:357–372. doi: 10.1006/jmbi.1993.1592. [DOI] [PubMed] [Google Scholar] source

In the paper

“TfR1 mRNA contains five iron-regulatory elements (IREs), which convey posttran-scriptional regulation of expression by cellular iron concentration (41).”

What the sources say

• Not checked yetcites [41] Casey JL. Hentze MW. Koeller DM. Caughman SW. Rouault TA. Klausner RD. Harford JB. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science. 1988;240:924–928. doi: 10.1126/science.2452485. [DOI] [PubMed] [Google Scholar]

In the paper

“As shown in Fig. 1, once Fe-Tf is bound to TfR1, the complex is endocytosed into the cell in an acidic endosome.”

In the paper

“When iron levels exceed the binding capacity of the available Tf, free circulating iron may be available as non-Tf-bound iron (NTBI).”

In the paper

“TfR2 has a lower affinity for Fe-Tf than does TfR1 (160, 320).”

What the sources say

• Not checked yetcites [160] Kawabata H. Yang R. Hirama T. Vuong PT. Kawano S. Gombart AF. Koeffler HP. Molecular cloning of transferrin receptor 2: a new member of the transferrin receptor-like family. J Biol Chem. 1999;274:20826–20832. doi: 10.1074/jbc.274.30.20826. [DOI] [PubMed] [Google Scholar] source
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In the paper

“TfR2 is primarily expressed in hepatocytes and in the iron-absorbing cells of the intestine and duodenum (35).”

What the sources say

• Not checked yetcites [35] Camaschella C. Roetto A. De Gobbi M. Genetic haemochromatosis: genes and mutations associated with iron loading. Best Pract Res Clin Haematol. 2002;15:261–276. doi: 10.1016/s1521-6926(02)90207-0. [DOI] [PubMed] [Google Scholar] source

In the paper

“IRP binding to an IRE in the 5′ UTR blocks the assembly of the 43S translation preinitiation complex (112).”

What the sources say

• Not checked yetcites [112] Gray NK. Hentze MW. Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs. EMBO J. 1994;13:3882–3891. doi: 10.1002/j.1460-2075.1994.tb06699.x. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“HFE-deficient mice developed severe iron overload and iron overload-related pathophysiology similar to that of humans with HH (336).”

What the sources say

• Not checked yetcites [336] Zhou XY. Tomatsu S. Fleming RE. Parkkila S. Waheed A. Jiang J. Fei Y. Brunt EM. Ruddy DA. Prass CE. Schatzman RC. O'Neill R. Britton RS. Bacon BR. Sly WS. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci U S A. 1998;95:2492–2497. doi: 10.1073/pnas.95.5.2492. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“In in vitro studies in hepatoma, K562, and HeLa cells, hypoxic conditions resulted in twofold to threefold increased TfR1 mRNA expression (190, 295).”

What the sources say

• Not checked yetcites [190] Lok CN. Ponka P. Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem. 1999;274:24147–24152. doi: 10.1074/jbc.274.34.24147. [DOI] [PubMed] [Google Scholar] source
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In the paper

“Recently, low levels of H2O2 were shown to increase TfR1 expression (8).”

What the sources say

• Not checked yetcites [8] Andriopoulos B. Hegedusch S. Mangin J. Riedel HD. Hebling U. Wang J. Pantopoulos K. Mueller S. Sustained hydrogen peroxide induces iron uptake by transferrin receptor-1 independent of the iron regulatory protein/iron-responsive element network. J Biol Chem. 2007;282:20301–20308. doi: 10.1074/jbc.M702463200. [DOI] [PubMed] [Google Scholar] source

In the paper

“Studies of TfR2 expression in a mouse model for hemochromatosis revealed that TfR2 was not downregulated in conditions of iron overload (90), supporting the absence of an iron-mediated posttranscriptional regulatory mechanism.”

What the sources say

• Not checked yetcites [90] Fleming RE. Migas MC. Holden CC. Waheed A. Britton RS. Tomatsu S. Bacon BR. Sly WS. Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proc Natl Acad Sci U S A. 2000;97:2214–2219. doi: 10.1073/pnas.040548097. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“A recent study suggests that the SLC39A zinc transporter, Zip14, may be involved in uptake of NTBI (188).”

What the sources say

• Not checked yetcites [188] Liuzzi JP. Aydemir F. Nam H. Knutson MD. Cousins RJ. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci U S A. 2006;103:13612–13617. doi: 10.1073/pnas.0606424103. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Two molecules of Fe-Tf bind to the TfR homodimer on a conserved argi-nine-glycine-aspartate sequence located in the helical domain of TfR (75).”

What the sources say

• Not checked yetcites [75] Dubljevic V. Sali A. Goding JW. A conserved RGD (Arg-Gly-Asp) motif in the transferrin receptor is required for binding to transferrin. Biochem J. 1999;341:11–14. [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Treatment of HepB3 human hepatoma cells with an iron chelator, desferrioxamine, increased transcription of TfR1 (21).”

What the sources say

• Not checked yetcites [21] Bianchi L. Tacchini L. Cairo G. HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation. Nucleic Acids Res. 1999;27:4223–4227. doi: 10.1093/nar/27.21.4223. [DOI] [PMC free article] [PubMed] [Google Scholar]

In the paper

“Individuals with iron-overload disorders such as HH or β-thalassemia may have plasma NTBI in the micromolar range (144).”

What the sources say

• Not checked yetcites [144] Jacobs EM. Hendriks JC. van Tits BL. Evans PJ. Breuer W. Liu DY. Jansen EH. Jauhiainen K. Sturm B. Porter JB. Scheiber-Mo-jdehkar B. von Bonsdorff L. Cabantchik ZI. Hider RC. Swinkels DW. Results of an international round robin for the quantification of serum non-transferrin-bound iron: need for defining standardization and a clinically relevant isoform. Anal Biochem. 2005;341:241–250. doi: 10.1016/j.ab.2005.03.008. [DOI] [PubMed] [Google Scholar] source

In the paper

“In this manner, HFE appears to block Tf binding to TfR through direct competition for the same binding site (179).”

What the sources say

• Not checked yetcites [179] Lebron JA. West AP Jr. Bjorkman PJ. The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor. J Mol Biol. 1999;294:239–245. doi: 10.1006/jmbi.1999.3252. [DOI] [PubMed] [Google Scholar] source

In the paper

“When iron concentrations are high, IRPs are degraded or inactivated, causing the downregulation of TfR1.”

In the paper

“In iron-replete cells, IRP1, which has ∼30% homology to mitochondrial aconitase based on amino acid alignments, loses its affinity for the IRE, and converts to a cytosolic aconitase (127, 263).”

What the sources say

• Not checked yetcites [127] Hentze MW. Argos P. Homology between IRE-BP, a regulatory RNA-binding protein, aconitase, and isopropylmalate isomerase. Nucleic Acids Res. 1991;19:1739–1740. doi: 10.1093/nar/19.8.1739. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper

“Expression of exogenous Fpn stimulates iron efflux (198).”

What the sources say

• Not checked yetcites [198] 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. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell. 2000;5:299–309. doi: 10.1016/s1097-2765(00)80425-6. [DOI] [PubMed] [Google Scholar] source

In the paper

“They also have high levels of iron in cells of the reticuloendothelial system as well as in hepatocytes, as a result of impaired iron efflux (123).”

What the sources say

• Not checked yetcites [123] Harris ZL. Durley AP. Man TK. Gitlin JD. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci U S A. 1999;96:10812–10817. doi: 10.1073/pnas.96.19.10812. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“In the intestine, where Cp is not expressed, Fpn couples with another multicopper oxidase, hephaestin (Heph) (313).”

What the sources say

• Not checked yetcites [313] Vulpe CD. Kuo YM. Murphy TL. Cowley L. Askwith C. Libina N. Gitschier J. Anderson GJ. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet. 1999;21:195–199. doi: 10.1038/5979. [DOI] [PubMed] [Google Scholar] source

In the paper

“DMT1 is critical to the export of iron released from Tf in the acidic endosome into the cytosol (see Fig. 1) (117).”

What the sources say

• Not checked yetcites [117] Gunshin H. Mackenzie B. Berger UV. Gunshin Y. Romero MF. Boron WF. Nussberger S. Gollan JL. Hediger MA. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997;388:482–488. doi: 10.1038/41343. [DOI] [PubMed] [Google Scholar] source

In the paper

“DCytb appears to be involved in the reduction of Fe3+ in the intestine, allowing it to be transported by DMT1 (197).”

What the sources say

• Not checked yetcites [197] 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. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science. 2001;291:1755–1759. doi: 10.1126/science.1057206. [DOI] [PubMed] [Google Scholar] source

In the paper

“Disruption of the sequence Y555XLXX in the cytoplasmic tail of DMT1 inhibited the localization of both DMT1A and DMT1B isoforms on the plasma membrane, but not in the endosome (286).”

What the sources say

• Not checked yetcites [286] Tabuchi M. Tanaka N. Nishida-Kitayama J. Ohno H. Kishi F. Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol Biol Cell. 2002;13:4371–4387. doi: 10.1091/mbc.E02-03-0165. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Fpn and Heph colocalize on the basolateral membrane of absorptive enterocytes of the duodenum and intestines (121).”

What the sources say

• Not checked yetcites [121] Han O. Kim EY. Colocalization of ferroportin-1 with hephaestin on the basolateral membrane of human intestinal absorptive cells. J Cell Biochem. 2007;101:1000–1010. doi: 10.1002/jcb.21392. [DOI] [PubMed] [Google Scholar] source

In the paper

“Heph was identified through study of sex-linked anemia (Sla) mice, which are deficient in transfer of iron absorbed in the intestines into the plasma (313).”

What the sources say

• Not checked yetcites [313] Vulpe CD. Kuo YM. Murphy TL. Cowley L. Askwith C. Libina N. Gitschier J. Anderson GJ. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet. 1999;21:195–199. doi: 10.1038/5979. [DOI] [PubMed] [Google Scholar] source

In the paper

“DMT1A was regulated by iron in human Caco-2 cells, a model system for intestinal iron absorption (see Fig. 2) (137).”

What the sources say

• Not checked yetcites [137] Hubert N. Hentze MW. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc Natl Acad Sci U S A. 2002;99:12345–12350. doi: 10.1073/pnas.192423399. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“DMT1 products include four different transcripts that occur as a result of alternative splicing at either the 3′ or 5′ end.”

What the sources say

• Not checked yetcites [137] Hubert N. Hentze MW. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc Natl Acad Sci U S A. 2002;99:12345–12350. doi: 10.1073/pnas.192423399. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Exogenous Fpn expressed in Xenopus oocytes served as a ferrous iron exporter (72).”

What the sources say

• Not checked yetcites [72] 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. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature. 2000;403:776–781. doi: 10.1038/35001596. [DOI] [PubMed] [Google Scholar] source

In the paper

“In a different pedigree of autosomal dominant hemochromatosis, another missense mutation of Fpn (N144H) was identified (218).”

What the sources say

• Not checked yetcites [218] Njajou OT. Vaessen N. Joosse M. Berghuis B. van Dongen JW. Breuning MH. Snijders PJ. Rutten WP. Sandkuijl LA. Oostra BA. van Duijn CM. Heutink P. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet. 2001;28:213–214. doi: 10.1038/90038. [DOI] [PubMed] [Google Scholar] source

In the paper

“Cp also functions as an antioxidant, because it converts Fe2+ to Fe3+, thereby decreasing the potential formation of reactive oxygen species (ROS) via Fenton chemistry (118).”

What the sources say

• Not checked yetcites [118] Gutteridge JM. Quinlan GJ. Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: the important primary role for iron-binding and iron-oxidising proteins. Biochim Biophys Acta. 1992;1159:248–254. doi: 10.1016/0167-4838(92)90052-f. [DOI] [PubMed] [Google Scholar] source

In the paper

“DMT1 is a metal-ion transporter with a uniquely broad range of divalent substrates such as Cd2+, Pb2+, Zn2+, Mn2+, Cu2+, and Co2+.”

In the paper

“Patients with the A77D mutation exhibit mainly early iron overload in the reticuloendocytic macrophages (205).”

What the sources say

• Not checked yetcites [205] Montosi G. Donovan A. Totaro A. Garuti C. Pignatti E. Cassanelli S. Trenor CC. Gasparini P. Andrews NC. Pietrangelo A. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest. 2001;108:619–623. doi: 10.1172/JCI13468. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“The authors concluded that the iron overload was a result of a gain-of-function mutation that would augment the iron-transport function of Fpn in enterocytes, thereby causing increased efflux of iron by the intestines (218).”

What the sources say

• Not checked yetcites [218] Njajou OT. Vaessen N. Joosse M. Berghuis B. van Dongen JW. Breuning MH. Snijders PJ. Rutten WP. Sandkuijl LA. Oostra BA. van Duijn CM. Heutink P. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet. 2001;28:213–214. doi: 10.1038/90038. [DOI] [PubMed] [Google Scholar] source

In the paper

“Further study revealed that regulation of DMT1 by iron is largely dependent on the cell line.”

In the paper

“In glioma cells, astrocytes, and macrophages, Fpn associates with ceruloplasmin (Cp) (123, 148).”

What the sources say

• Not checked yetcites [123] Harris ZL. Durley AP. Man TK. Gitlin JD. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci U S A. 1999;96:10812–10817. doi: 10.1073/pnas.96.19.10812. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper

“In mice, hepcidin was required for the development of anemia during inflammation (214).”

What the sources say

• Not checked yetcites [214] Nemeth E. Rivera S. Gabayan V. Keller C. Taudorf S. Pedersen BK. Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271–1276. doi: 10.1172/JCI20945. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“the upregulation of hepcidin during inflammation (a precipitating event in the development of hypoferremia) occurs, at least in part, through the action of IL-6 (214).”

What the sources say

• Not checked yetcites [214] Nemeth E. Rivera S. Gabayan V. Keller C. Taudorf S. Pedersen BK. Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271–1276. doi: 10.1172/JCI20945. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Its expression is increased in response to iron and inflammation (247)”

What the sources say

• Not checked yetcites [247] Pigeon C. Ilyin G. Courselaud B. Leroyer P. Turlin B. Brissot P. Loreal O. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811–7819. doi: 10.1074/jbc.M008923200. [DOI] [PubMed] [Google Scholar] source

In the paper

“An alternative mechanism of hepcidin regulation through a signaling pathway involving hemojuvelin (HFE2, also known as HJV) and bone morphogenetic proteins (BMP) was recently identified (14).”

What the sources say

• Not checked yetcites [14] Babitt JL. Huang FW. Wrighting DM. Xia Y. Sidis Y. Samad TA. Campagna JA. Chung RT. Schneyer AL. Woolf CJ. Andrews NC. Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539. doi: 10.1038/ng1777. [DOI] [PubMed] [Google Scholar] source

In the paper

“Activation of STAT3 transcription factor by IL-6 results in the transactivation of a STAT binding sequence in the hepcidin promoter (245, 310).”

What the sources say

• Not checked yetcites [245] Pietrangelo A. Dierssen U. Valli L. Garuti C. Rump A. Corradini E. Ernst M. Klein C. Trautwein C. STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterology. 2007;132:294–300. doi: 10.1053/j.gastro.2006.10.018. [DOI] [PubMed] [Google Scholar] source
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In the paper

“It negatively regulates iron efflux by binding Fpn and triggering its internalization and subsequent degradation (215).”

What the sources say

• Not checked yetcites [215] Nemeth E. Tuttle MS. Powelson J. Vaughn MB. Donovan A. Ward DM. Ganz T. Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–2093. doi: 10.1126/science.1104742. [DOI] [PubMed] [Google Scholar] source

In the paper

“suggesting that C/EBPα modulates hepcidin transcription (58).”

What the sources say

• Not checked yetcites [58] Courselaud B. Pigeon C. Inoue Y. Inoue J. Gonzalez FJ. Leroyer P. Gilot D. Boudjema K. Guguen-Guillouzo C. Brissot P. Loreal O. Ilyin G. C/EBPalpha 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. 2002;277:41163–41170. doi: 10.1074/jbc.M202653200. [DOI] [PubMed] [Google Scholar] source

In the paper

“mice deficient in C/EBPα exhibited lower levels of hepcidin mRNA,”

What the sources say

• Not checked yetcites [58] Courselaud B. Pigeon C. Inoue Y. Inoue J. Gonzalez FJ. Leroyer P. Gilot D. Boudjema K. Guguen-Guillouzo C. Brissot P. Loreal O. Ilyin G. C/EBPalpha 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. 2002;277:41163–41170. doi: 10.1074/jbc.M202653200. [DOI] [PubMed] [Google Scholar] source

In the paper

“The 5′ UTR of Fpn mRNA contains an IRE (198).”

What the sources say

• Not checked yetcites [198] 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. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell. 2000;5:299–309. doi: 10.1016/s1097-2765(00)80425-6. [DOI] [PubMed] [Google Scholar] source

In the paper

“Mutation of two adjacent tyrosine residues at the phosphorylation site blocks internalization.”

What the sources say

• Not checked yetcites [66] De Domenico I. Ward DM. Langelier C. Vaughn MB. Nemeth E. Sundquist WI. Ganz T. Musci G. Kaplan J. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell. 2007;18:2569–2578. doi: 10.1091/mbc.E07-01-0060. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“The mRNA of hepcidin does not contain this element (99),”

What the sources say

• Not checked yetcites [99] Ganz T. Nemeth E. Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol. 2006;290:G199–G203. doi: 10.1152/ajpgi.00412.2005. [DOI] [PubMed] [Google Scholar] source

In the paper

“Studies in the liver demonstrated that C/EBPα plays a role in the iron-mediated regulation of hepcidin mRNA (58).”

What the sources say

• Not checked yetcites [58] Courselaud B. Pigeon C. Inoue Y. Inoue J. Gonzalez FJ. Leroyer P. Gilot D. Boudjema K. Guguen-Guillouzo C. Brissot P. Loreal O. Ilyin G. C/EBPalpha 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. 2002;277:41163–41170. doi: 10.1074/jbc.M202653200. [DOI] [PubMed] [Google Scholar] source

In the paper

“Tissue-specific overexpression of hepcidin in murine liver resulted in body iron deficiency and severe microcytic hypochromic anemia of mice at birth (216).”

What the sources say

• Not checked yetcites [216] Nicolas G. Chauvet C. Viatte L. Danan JL. Bigard X. Devaux I. Beaumont C. Kahn A. Vaulont S. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110:1037–1044. doi: 10.1172/JCI15686. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“suggesting that a sensor other than the IRE-IRP system may be necessary to regulate hepcidin translation in response to iron concentrations.”

In the paper

“hepcidin mRNA was increased in the murine liver and in hepatocytes in response to stimulation with LPS (247).”

What the sources say

• Not checked yetcites [247] Pigeon C. Ilyin G. Courselaud B. Leroyer P. Turlin B. Brissot P. Loreal O. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811–7819. doi: 10.1074/jbc.M008923200. [DOI] [PubMed] [Google Scholar] source

In the paper

“This ubiquitination results in the subsequent degradation of Fpn.”

What the sources say

• Not checked yetcites [65] De Domenico I. Ward DM. di Patti MC. Jeong SY. David S. Musci G. Kaplan J. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J. 2007;26:2823–2831. doi: 10.1038/sj.emboj.7601735. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Administration of synthetic hepcidin induced rapid decline in serum iron levels (hypoferremia) in mice (258).”

What the sources say

• Not checked yetcites [258] Rivera S. Nemeth E. Gabayan V. Lopez MA. Farshidi D. Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood. 2005;106:2196–2199. doi: 10.1182/blood-2005-04-1766. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“After hepcidin binding, Fpn is tyrosine phosphorylated on the plasma membrane (66).”

What the sources say

• Not checked yetcites [66] De Domenico I. Ward DM. Langelier C. Vaughn MB. Nemeth E. Sundquist WI. Ganz T. Musci G. Kaplan J. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell. 2007;18:2569–2578. doi: 10.1091/mbc.E07-01-0060. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Iron overload induces hepcidin mRNA in hepatocytes (247);”

What the sources say

• Not checked yetcites [247] Pigeon C. Ilyin G. Courselaud B. Leroyer P. Turlin B. Brissot P. Loreal O. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811–7819. doi: 10.1074/jbc.M008923200. [DOI] [PubMed] [Google Scholar] source

In the paper

“and decreased by hypoxia and anemia (216).”

What the sources say

• Not checked yetcites [216] Nicolas G. Chauvet C. Viatte L. Danan JL. Bigard X. Devaux I. Beaumont C. Kahn A. Vaulont S. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110:1037–1044. doi: 10.1172/JCI15686. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Such an IRE in the 5′ UTR of mRNA is also located in other genes involved in the regulation of iron levels in the cell, including ferritin (heavy and light chains) and eALAS, which is involved in heme synthesis in erythroid cells (see Fig. 2) (131).”

What the sources say

• Not checked yetcites [131] Hentze MW. Muckenthaler MU. Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell. 2004;117:285–297. doi: 10.1016/s0092-8674(04)00343-5. [DOI] [PubMed] [Google Scholar] source

In the paper

“levels of C/EBPα transcription factor in murine liver are doubled in response to iron loading,”

What the sources say

• Not checked yetcites [58] Courselaud B. Pigeon C. Inoue Y. Inoue J. Gonzalez FJ. Leroyer P. Gilot D. Boudjema K. Guguen-Guillouzo C. Brissot P. Loreal O. Ilyin G. C/EBPalpha 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. 2002;277:41163–41170. doi: 10.1074/jbc.M202653200. [DOI] [PubMed] [Google Scholar] source

In the paper

“Several lines of evidence indicate that hepcidin is a negative regulator of plasma iron.”

In the paper

“Disruption of murine Heph and Cp genes resulted in increasing retinal iron concentrations with age that caused pathologic changes reminiscent of those seen in human aceruloplasminemia (119).”

What the sources say

• Not checked yetcites [119] Hahn P. Qian Y. Dentchev T. Chen L. Beard J. Harris ZL. Dunaief JL. Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration. Proc Natl Acad Sci U S A. 2004;101:13850–13855. doi: 10.1073/pnas.0405146101. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Fpn is posttranslationally regulated by a peptide hormone, hepcidin (215).”

What the sources say

• Not checked yetcites [215] Nemeth E. Tuttle MS. Powelson J. Vaughn MB. Donovan A. Ward DM. Ganz T. Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–2093. doi: 10.1126/science.1104742. [DOI] [PubMed] [Google Scholar] source

In the paper

“This study showed that BMP could upregulate hepcidin in hepatocytes.”

What the sources say

• Not checked yetcites [14] Babitt JL. Huang FW. Wrighting DM. Xia Y. Sidis Y. Samad TA. Campagna JA. Chung RT. Schneyer AL. Woolf CJ. Andrews NC. Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539. doi: 10.1038/ng1777. [DOI] [PubMed] [Google Scholar] source

In the paper

“The mechanism by which IL-6 induces hepcidin mRNA involves the activation of STAT3 (324).”

What the sources say

• Not checked yetcites [324] Wrighting DM. Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood. 2006;108:3204–3209. doi: 10.1182/blood-2006-06-027631. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“in hepatocytes derived from HIF-1α-knockout mice, hepcidin expression in response to iron deficiency was increased (242).”

What the sources say

• Not checked yetcites [242] Peyssonnaux C. Zinkernagel AS. Schuepbach RA. Rankin E. Vaulont S. Haase VH. Nizet V. Johnson RS. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs) J Clin Invest. 2007;117:1926–1932. doi: 10.1172/JCI31370. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“In the brain, the oligodendrocytes, microglia, and neurons express ferritin (53).”

What the sources say

• Not checked yetcites [53] Connor JR. Boeshore KL. Benkovic SA. Menzies SL. Isoforms of ferritin have a specific cellular distribution in the brain. J Neurosci Res. 1994;37:461–465. doi: 10.1002/jnr.490370405. [DOI] [PubMed] [Google Scholar] source

In the paper

“downstream activation of Smad4 was required for BMP-mediated hepcidin upregulation,”

What the sources say

• Not checked yetcites [14] Babitt JL. Huang FW. Wrighting DM. Xia Y. Sidis Y. Samad TA. Campagna JA. Chung RT. Schneyer AL. Woolf CJ. Andrews NC. Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539. doi: 10.1038/ng1777. [DOI] [PubMed] [Google Scholar] source

In the paper

“Induction by administration of exogenous BMPs was greater than that caused by treatment with LPS (300).”

What the sources say

• Not checked yetcites [300] Truksa J. Peng H. Lee P. Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A. 2006;103:10289–10293. doi: 10.1073/pnas.0603124103. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“HIF-1α was shown to bind to TfR1 HRE.”

What the sources say

• Not checked yetcites [242] Peyssonnaux C. Zinkernagel AS. Schuepbach RA. Rankin E. Vaulont S. Haase VH. Nizet V. Johnson RS. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs) J Clin Invest. 2007;117:1926–1932. doi: 10.1172/JCI31370. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“More recently, BMP9, BMP4, and BMP2 were identified as inducers of hepcidin (300).”

What the sources say

• Not checked yetcites [300] Truksa J. Peng H. Lee P. Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A. 2006;103:10289–10293. doi: 10.1073/pnas.0603124103. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Murine erythroleukemia cells that overexpress ferritin H displayed lower levels of the labile iron pool and ROS (78).”

What the sources say

• Not checked yetcites [78] Epsztejn S. Glickstein H. Picard V. Slotki IN. Breuer W. Beaumont C. Cabantchik ZI. H-ferritin subunit overexpression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood. 1999;94:3593–3603. [PubMed] [Google Scholar] source

In the paper

“The H subunit has ferroxidase activity, which converts Fe2+ to Fe3+ for storage inside the shell (178)”

What the sources say

• Not checked yetcites [178] Lawson DM. Treffry A. Artymiuk PJ. Harrison PM. Yewdall SJ. Luzzago A. Cesareni G. Levi S. Arosio P. Identification of the ferroxidase centre in ferritin. FEBS Lett. 1989;254:207–210. doi: 10.1016/0014-5793(89)81040-3. [DOI] [PubMed] [Google Scholar] source

In the paper

“BMP-mediated induction of hepcidin was similar in wild-type congenic strains, and IL-6 knockout, HFE knockout, and TfR2 mutant mice,”

What the sources say

• Not checked yetcites [300] Truksa J. Peng H. Lee P. Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A. 2006;103:10289–10293. doi: 10.1073/pnas.0603124103. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“HIF-1 appears to function as a negative regulator of hepcidin expression:”

In the paper

“When ferritin H was transgenically overexpressed into Parkinson disease (PD) model mice, reduced oxidative stress was found (159).”

What the sources say

• Not checked yetcites [159] Kaur D. Yantiri F. Rajagopalan S. Kumar J. Mo JQ. Boonplueang R. Viswanath V. Jacobs R. Yang L. Beal MF. DiMonte D. Volitaskis I. Ellerby L. Cherny RA. Bush AI. Andersen JK. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron. 2003;37:899–909. doi: 10.1016/s0896-6273(03)00126-0. [DOI] [PubMed] [Google Scholar] source

In the paper

“None of the ferritin H-deficient mice survived past embryonic day 9.5 (85).”

What the sources say

• Not checked yetcites [85] Ferreira C. Bucchini D. Martin ME. Levi S. Arosio P. Grand-champ B. Beaumont C. Early embryonic lethality of H ferritin gene deletion in mice. J Biol Chem. 2000;275:3021–3024. doi: 10.1074/jbc.275.5.3021. [DOI] [PubMed] [Google Scholar] source

In the paper

“Ferritin is found in the cytoplasm, nucleus, and mitochondria of cells (summarized in Table 1).”

What the sources say

• Not checked yetcites Table 1

In the paper

“The ratio of H and L subunits in the ferritin protein is not fixed and is tissue dependent (10).”

What the sources say

• Not checked yetcites [10] Arosio P. Yokota M. Drysdale JW. Structural and immunological relationships of isoferritins in normal and malignant cells. Cancer Res. 1976;36:1735–1739. [PubMed] [Google Scholar]

In the paper

“when HeLa cells stably transfected with tetracycline-inducible ferritin H and L were forced to overexpress ferritin, the accumulation of H2O2-induced ROS was reduced (59).”

What the sources say

• Not checked yetcites [59] Cozzi A. Corsi B. Levi S. Santambrogio P. Albertini A. Arosio P. Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity. J Biol Chem. 2000;275:25122–25129. doi: 10.1074/jbc.M003797200. [DOI] [PubMed] [Google Scholar] source

In the paper

“suggesting that BMP-mediated activation of hepcidin expression may not require these proteins (300).”

What the sources say

• Not checked yetcites [300] Truksa J. Peng H. Lee P. Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A. 2006;103:10289–10293. doi: 10.1073/pnas.0603124103. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“HIF-1 has been implicated in the transcriptional regulation of hepcidin in response to hypoxia (242).”

What the sources say

• Not checked yetcites [242] Peyssonnaux C. Zinkernagel AS. Schuepbach RA. Rankin E. Vaulont S. Haase VH. Nizet V. Johnson RS. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs) J Clin Invest. 2007;117:1926–1932. doi: 10.1172/JCI31370. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Overexpression of HFE2 enhanced hepcidin production.”

What the sources say

• Not checked yetcites [14] Babitt JL. Huang FW. Wrighting DM. Xia Y. Sidis Y. Samad TA. Campagna JA. Chung RT. Schneyer AL. Woolf CJ. Andrews NC. Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539. doi: 10.1038/ng1777. [DOI] [PubMed] [Google Scholar] source

In the paper

“Deletion of ferritin H in mice is embryonically lethal between 3.5 and 9.5 days of gestation (85).”

What the sources say

• Not checked yetcites [85] Ferreira C. Bucchini D. Martin ME. Levi S. Arosio P. Grand-champ B. Beaumont C. Early embryonic lethality of H ferritin gene deletion in mice. J Biol Chem. 2000;275:3021–3024. doi: 10.1074/jbc.275.5.3021. [DOI] [PubMed] [Google Scholar] source

In the paper

“Accumulating evidence shows that ferritin acts as an antioxidant protein (59, 60, 78, 159, 227, 243).”

What the sources say

• Not checked yetcites [59] Cozzi A. Corsi B. Levi S. Santambrogio P. Albertini A. Arosio P. Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity. J Biol Chem. 2000;275:25122–25129. doi: 10.1074/jbc.M003797200. [DOI] [PubMed] [Google Scholar] source
• Not checked yetcites [60] Cozzi A. Corsi B. Levi S. Santambrogio P. Biasiotto G. Arosio P. Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin. Blood. 2004;103:2377–2383. doi: 10.1182/blood-2003-06-1842. [DOI] [PubMed] [Google Scholar] source
• Not checked yetcites [78] Epsztejn S. Glickstein H. Picard V. Slotki IN. Breuer W. Beaumont C. Cabantchik ZI. H-ferritin subunit overexpression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood. 1999;94:3593–3603. [PubMed] [Google Scholar] source

In the paper

“hepatocytes deficient in HFE2 had impaired hepcidin induction by BMP signaling (14).”

What the sources say

• Not checked yetcites [14] Babitt JL. Huang FW. Wrighting DM. Xia Y. Sidis Y. Samad TA. Campagna JA. Chung RT. Schneyer AL. Woolf CJ. Andrews NC. Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38:531–539. doi: 10.1038/ng1777. [DOI] [PubMed] [Google Scholar] source

In the paper

“The gram-negative diplococcus, Neisseria meningitidis, rapidly induced ferritin degradation by the activation of the autophagy system, which allows meningococci replication in infected epithelial cells (173).”

What the sources say

• Not checked yetcites [173] Larson JA. Howie HL. So M. Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source. Mol Microbiol. 2004;53:807–820. doi: 10.1111/j.1365-2958.2004.04169.x. [DOI] [PubMed] [Google Scholar] source

In the paper

“the recombinant ferritin H protein was reported to activate T cells (111).”

What the sources say

• Not checked yetcites [111] Gray CP. Arosio P. Hersey P. Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells. Blood. 2002;99:3326–3334. doi: 10.1182/blood.v99.9.3326. [DOI] [PubMed] [Google Scholar] source

In the paper

“mitochondrial ferritin genes do not have IRE in both the human and the mouse (74, 182).”

What the sources say

• Not checked yetcites [74] Drysdale J. Arosio P. Invernizzi R. Cazzola M. Volz A. Corsi B. Biasiotto G. Levi S. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol Dis. 2002;29:376–383. doi: 10.1006/bcmd.2002.0577. [DOI] [PubMed] [Google Scholar] source
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In the paper

“and enhances ferritin degradation (64).”

What the sources say

• Not checked yetcites [64] De Domenico I. Vaughn MB. Li L. Bagley D. Musci G. Ward DM. Kaplan J. Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J. 2006;25:5396–5404. doi: 10.1038/sj.emboj.7601409. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“binding of ferritin L to the cell surface of liver, T-, and B-lymphoid cells was demonstrated (7, 208)”

What the sources say

• Not checked yetcites [7] Anderson GJ. Faulk WP. Arosio P. Moss D. Powell LW. Halliday JW. Identification of H- and L-ferritin subunit binding sites on human T and B lymphoid cells. Br J Haematol. 1989;73:260–264. doi: 10.1111/j.1365-2141.1989.tb00262.x. [DOI] [PubMed] [Google Scholar] source
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In the paper

“increased expression of mitochondrial ferritin in refractory anemia with ringed sideroblastic erythroblasts has been described at a very early stage of erythroid differentiation and is correlated with β-globin and GATA-1 induction involved in this process (288).”

What the sources say

• Not checked yetcites [288] Tehranchi R. Invernizzi R. Grandien A. Zhivotovsky B. Fadeel B. Forsblom AM. Travaglino E. Samuelsson J. Hast R. Nilsson L. Cazzola M. Wibom R. Hellstrom-Lindberg E. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Blood. 2005;106:247–253. doi: 10.1182/blood-2004-12-4649. [DOI] [PubMed] [Google Scholar] source

In the paper

“Mouse T-cell immunoglobulin-domain and mucin-domain (TIM)-2 was identified as a ferritin H subunit receptor (48)”

What the sources say

• Not checked yetcites [48] 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. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med. 2005;202:955–965. doi: 10.1084/jem.20042433. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“ferritin H disruption by siRNA sensitized the cells to H2O2-induced oxidative stress (60)”

What the sources say

• Not checked yetcites [60] Cozzi A. Corsi B. Levi S. Santambrogio P. Biasiotto G. Arosio P. Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin. Blood. 2004;103:2377–2383. doi: 10.1182/blood-2003-06-1842. [DOI] [PubMed] [Google Scholar] source

In the paper

“The functional elements of mitochondrial ferritin are similar to those of ferritin H, including ferroxidase activity and metal-binding sites (172)”

What the sources say

• Not checked yetcites [172] Langlois d'Estaintot B. Santambrogio P. Granier T. Gallois B. Chevalier JM. Precigoux G. Levi S. Arosio P. Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. J Mol Biol. 2004;340:277–293. doi: 10.1016/j.jmb.2004.04.036. [DOI] [PubMed] [Google Scholar] source

In the paper

“Mitochondrial ferritin is highly conserved among a wide variety of living creatures, including Drosophila (204, 332) and plants (204, 332)”

What the sources say

• Not checked yetcites [204] Missirlis F. Holmberg S. Georgieva T. Dunkov BC. Rouault TA. Law JH. Characterization of mitochondrial ferritin in Drosophila. Proc Natl Acad Sci U S A. 2006;103:5893–5898. doi: 10.1073/pnas.0601471103. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper

“Proteasome-mediated ferritin degradation has also been reported (199, 255).”

What the sources say

• Not checked yetcites [199] Mehlhase J. Sandig G. Pantopoulos K. Grune T. Oxidation-induced ferritin turnover in microglial cells: role of proteasome. Free Radic Biol Med. 2005;38:276–285. doi: 10.1016/j.freeradbiomed.2004.10.025. [DOI] [PubMed] [Google Scholar] source
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In the paper

“Ferritin H incorporation was not observed in the absence of TIM-2 (48).”

What the sources say

• Not checked yetcites [48] 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. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med. 2005;202:955–965. doi: 10.1084/jem.20042433. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“TIM-2-deficient mice showed increased levels of cytokines IL-4, IL-5, IL-6, and IL-10, which may result in increased inflammation (256).”

What the sources say

• Not checked yetcites [256] Rennert PD. Ichimura T. Sizing ID. Bailly V. Li Z. Rennard R. McCoon P. Pablo L. Miklasz S. Tarilonte L. Bonventre JV. T cell, Ig domain, mucin domain-2 gene-deficient mice reveal a novel mechanism for the regulation of Th2 immune responses and airway inflammation. J Immunol. 2006;177:4311–4321. doi: 10.4049/jimmunol.177.7.4311. [DOI] [PubMed] [Google Scholar] source

In the paper

“Only monoubiquitinated ferritin was reported in an Fpn-overexpression experiment (64).”

What the sources say

• Not checked yetcites [64] De Domenico I. Vaughn MB. Li L. Bagley D. Musci G. Ward DM. Kaplan J. Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J. 2006;25:5396–5404. doi: 10.1038/sj.emboj.7601409. [DOI] [PMC free article] [PubMed] [Google Scholar] source

In the paper

“Elevated serum ferritin H levels were shown to be correlated with increased CD4+, CD25+, CD69− regulatory T cells (110).”

What the sources say

• Not checked yetcites [110] Gray CP. Arosio P. Hersey P. Association of increased levels of heavy-chain ferritin with increased CD4+ CD25+ regulatory T-cell levels in patients with melanoma. Clin Cancer Res. 2003;9:2551–2559. [PubMed] [Google Scholar] source

In the paper

“Over-expression of Fpn accelerates export of cytosolic iron (215)”

What the sources say

• Not checked yetcites [215] Nemeth E. Tuttle MS. Powelson J. Vaughn MB. Donovan A. Ward DM. Ganz T. Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–2093. doi: 10.1126/science.1104742. [DOI] [PubMed] [Google Scholar] source