Iron is a crucial factor for life. However, it also has the potential to cause the formation of noxious free radicals. These double-edged sword characteristics demand a tight regulation of cellular iron metabolism. In this review, we discuss the various pathways of cellular iron uptake, cellular iron storage, and transport. Recent advances in understanding the reduction and uptake of non-transferrin-bound iron are discussed. We also discuss the recent progress in the understanding of transcriptional and translational regulation by iron. Furthermore, we discuss recent advances in the understanding of the regulation of cellular and systemic iron homeostasis and several key diseases resulting from iron deficiency and overload. We also discuss the knockout mice available for studying iron metabolism and the related human conditions. Antioxid. Redox Signal. 18, 2473–2507.
AbboudS, HaileDJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem, 275:19906–19912. 2000.
2.
AisenP, ListowskyI. Iron transport and storage proteins. Annu Rev Biochem, 49:357–393. 1980.
3.
AisenP, LeibmanA, ZweierJ. Stoichiometric and site characteristics of the binding of iron to human transferrin. J Biol Chem, 253:1930–1937. 1978.
4.
AndersonGJ. Ironing out disease: inherited disorders of iron homeostasis. IUBMB Life, 51:11–17. 2001.
5.
AndrewsNC. Forging a field: the golden age of iron biology. Blood, 112:219–230. 2008.
6.
AndrewsSC. The ferritin-like superfamily: evolution of the biological iron storeman from a rubrerythrin-like ancestor. Biochim Biophys Acta, 1800:691–705. 2010.
7.
AndriopoulosBJr., CorradiniE, XiaY, FaasseSA, ChenS, GrgurevicL, KnutsonMD, PietrangeloA, VukicevicS, LinHY, BabittJL. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet, 41:482–487. 2009.
8.
ArndtS, MaegdefrauU, DornC, SchardtK, HellerbrandC, BosserhoffA-K. Iron-induced expression of bone morphogenic protein 6 in intestinal cells is the main regulator of hepatic hepcidin expression in vivo. Gastroenterology, 138:372–382. 2010.
9.
ArosioP, IngrassiaR, CavadiniP. Ferritins: a family of molecules for iron storage, antioxidation and more. Biochim Biophys Acta, 1790:589–599. 2008.
10.
AtanassovaBD, TzatchevKN. Ascorbic acid—important for iron metabolism. Folia Med (Plovdiv), 50:11–16. 2008.
11.
AttiehZK, MukhopadhyayCK, SeshadriV, TripoulasNA, FoxPL. Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism. J Biol Chem, 274:1116–1123. 1999.
12.
AttisanoL, WranaJL. Mads and Smads in TGFβ signalling. Curr Opin Cell Biol, 10:188–194. 1998.
13.
BabittJL, HuangFW, WrightingDM, XiaY, SidisY, SamadTA, CampagnaJA, ChungRT, SchneyerAL, WoolfCJ, AndrewsNC, LinHY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet, 38:531–539. 2006.
14.
BabittJL, HuangFW, XiaY, SidisY, AndrewsNC, LinHY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest, 117:1933–1939. 2007.
BakerE, BakerSM, MorganEH. Characterisation of non-transferrin-bound iron (ferric citrate) uptake by rat hepatocytes in culture. Biochim Biophys Acta, 1380:21–30. 1998.
17.
BakerMA, LawenA. The function of the plasma membrane NADH-oxidoreductase system. A critical review of the structural and functional data. Antioxid Redox Signal, 2:197–212. 2000.
18.
BarnhamKJ, BushAI. Metals in Alzheimer's and Parkinson's diseases. Curr Opin Chem Biol, 12:222–228. 2008.
19.
BéliveauF, BruléC, DésiletsA, ZimmermanB, LaporteSA, LavoieCL, LeducR. Essential role of endocytosis of the type II transmembrane serine protease TMPRSS6 in regulating its functionality. J Biol Chem, 286:29035–29043. 2011.
20.
BennettMJ, LebrónJA, BjorkmanPJ. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature, 403:46–53. 2000.
21.
BeutlerE. Hemochromatosis: genetics and pathophysiology. Annu Rev Med, 57:331–347. 2006.
22.
BeutlerL, BeutlerE. Hematologically important mutations: iron storage diseases. Blood Cells Mol Dis, 33:40–44. 2004.
23.
BianchiL, TacchiniL, CairoG. HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation. Nucl Acid Res, 27:4223–4227. 1999.
24.
BishopGM, ScheiberIF, DringenR, RobinsonSR. Synergistic accumulation of iron and zinc by cultured astrocytes. J Neural Transm, 117:809–817. 2010.
25.
BishopGM, DangTN, DringenR, RobinsonSR. Accumulation of non-transferrin-bound iron by neuons, astrocytes, and microglia. Neurotox Res, 19:443–451. 2011.
26.
BomfordA, YoungSP, WilliamsR. Release of iron from the two iron-binding sites of transferrin by cultured human cells: modulation by methylamine. Biochemistry, 24:3472–3478. 1985.
27.
BothwellTH. The control of iron absorption. Br J Haematol, 14:453–456. 1968.
28.
Bou-AbdallahF. The iron redox and hydrolysis chemistry of the ferritins. Biochim Biophys Acta, 1800:719–731. 2010.
29.
BourdonE, KangDK, GhoshMC, DrakeSK, WeyJ, LevineRL, RouaultTA. The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2. Blood Cells Mol Dis, 31:247–255. 2003.
30.
BoutonC, DrapierJC. Iron regulatory proteins as NO signal transducers. Sci STKE, 2003:pe17. 2003.
31.
BradburyMWB. Transport of iron in the blood–brain–cerebrospinal fluid system. J Neurochem, 69:443–454. 1997.
32.
Brasse-LagnelC, KarimZ, LetteronP, BekriS, BadoA, BeaumontC. Intestinal DMT1 cotransporter is down-regulated by hepcidin via proteasome internalization and degradation. Gastroenterology, 140:1261–1271.e1. 2011.
33.
BratosinD, MazurierJ, TissierJP, EstaquierJ, HuartJJ, AmeisenJC, AminoffD, MontreuilJ. Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review. Biochimie, 80:173–195. 1998.
BullenJJ, SpaldingPB, WardCG, GutteridgeJM. Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Arch Intern Med, 151:1606–1609. 1991.
39.
BurdoJR, AntonettiDA, WolpertEB, ConnorJR. Mchanisms and regulation of transferrin and iron transport in a model blood–brain barrier system. Neuroscience, 121:883–890. 2003.
40.
BurkittMJ, GilbertBC. Model studies of the iron-catalysed Haber-Weiss cycle and the ascorbate-driven Fenton reaction. Free Radic Res Commun, 10:265–280. 1990.
41.
CaiCX, LinsenmayerTF. Nuclear translocation of ferritin in corneal epithelial cells. J Cell Sci, 114:2327–2334. 2001.
42.
CaiCX, BirkDE, LinsenmayerTF. Nuclear ferritin protects DNA from UV damage in corneal epithelial cells. Mol Biol Cell, 9:1037–1051. 1998.
43.
CairoG, RecalcatiS, MantovaniA, LocatiM. Iron trafficking and metabolism in macrophages: contribution to the polarized phenotype. Trends Immunol, 32:241–247. 2011.
44.
CaltagironeA, WeissG, PantopoulosK. Modulation of cellular iron metabolism by hydrogen peroxide. Effects of H2O2 on the expression and function of iron-responsive element-containing mRNAs in B6 fibroblasts. J Biol Chem, 276:19738–19745. 2001.
45.
CalzolariA, RaggiC, DeaglioS, SposiNM, StafsnesM, FecchiK, ParoliniI, MalavasiF, PeschleC, SargiacomoM, TestaU. TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway. J Cell Sci, 119:4486–4498. 2006.
CamaschellaC, RoettoA, De GobbiM. Juvenile hemochromatosis. Semin Hematol, 39:242–248. 2002.
48.
CampanellaA, IsayaG, O'NeillHA, SantambrogioP, CozziA, ArosioP, LeviS. The expression of human mitochondrial ferritin rescues respiratory function in frataxin-deficient yeast. Hum Mol Genet, 13:2279–2288. 2004.
49.
CaseyJL, KoellerDM, RaminVC, KlausnerRD, HarfordJB. Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3′ untranslated region of the mRNA. EMBO J, 8:3693–3699. 1989.
ChallisGL. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem, 6:601–611. 2005.
52.
ChenW, DaileyHA, PawBH. Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis. Blood, 116:628–630. 2010.
53.
ChenD, ZhaoM, MundyGR. Bone morphogenetic proteins. Growth Factors, 22:233–241. 2004.
54.
ChenJ, EnnsCA. The cytoplasmic domain of transferrin receptor 2 dictates its stability and response to holo-transferrin in Hep3B cells. J Biol Chem, 282:6201–6209. 2007.
55.
ChenJ, ChloupkovaM, GaoJ, Chapman-ArvedsonTL, EnnsCA. HFE modulates transferrin receptor 2 levels in hepatoma cells via interactions that differ from transferrin receptor 1-HFE interactions. J Biol Chem, 282:36862–36870. 2007.
56.
ChenW, HuangFW, de RenshawTB, AndrewsNC. Skeletal muscle hemojuvelin is dispensable for systemic iron homeostasis. Blood, 117:6319–6325. 2011.
57.
ChenL, ZhangX, Chen-RoetlingJ, ReganRF. Increased striatal injury and behavioral deficits after intracerebral hemorrhage in hemopexin knockout mice. J Neurosurg, 114:1159–1167. 2011.
58.
ChenOS, SchalinskeKL, EisensteinRS. Dietary iron intake modulates the activity of iron regulatory proteins and the abundance of ferritin and mitochondrial aconitase in rat liver. J Nutr, 127:238–248. 1997.
59.
ChengY, ZakO, AisenP, HarrisonSC, WalzT. Structure of the human transferrin receptor-transferrin complex. Cell, 116:565–576. 2004.
60.
ChepelevNL, WillmoreWG. Regulation of iron pathways in response to hypoxia. Free Radic Biol Med, 50:645–666. 2011.
61.
ChloupkováM, ZhangA-S, EnnsCA. Stoichiometries of transferrin receptors 1 and 2 in human liver. Blood Cells Mol Dis, 44:28–33. 2010.
62.
ChuaAC, GrahamRM, TrinderD, OlynykJK. The regulation of cellular iron metabolism. Crit Rev Clin Lab Sci, 44:413–459. 2007.
63.
This reference has been deleted.
64.
ClarkNG, SheardNF, KelleherJF. Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency. Nutr Rev, 50:134–137. 1992.
65.
ClarkSF. Iron deficiency anemia. Nutr Clin Pract, 23:128–141. 2008.
66.
ClarkeSL, VasanthakumarA, AndersonSA, PondarreC, KohCM, DeckKM, PitulaJS, EpsteinCJ, FlemingMD, EisensteinRS. Iron-responsive degradation of iron-regulatory protein 1 does not require the iron-S cluster. EMBO J, 25:544–553. 2006.
67.
CmejlaR, PetrakJ, CmejlovaJ. A novel iron responsive element in the 3′UTR of human MRCKαBiochem Biophys Res Commun, 341:158–166. 2006.
68.
CockmanME, MassonN, MoleDR, JaakkolaP, ChangG-W, CliffordSC, MaherER, PughCW, RatcliffePJ, MaxwellPH. Hypoxia inducible factor-α binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem, 275:25733–25741. 2000.
69.
ConradME, UmbreitJN. Iron absorption and transport: an update. Am J Hematol, 64:287–298. 2000.
70.
ConradME, UmbreitJN, MooreEG, HainsworthLN, PorubcinM, SimovichMJ, NakadaMT, DolanK, GarrickMD. Separate pathways for cellular uptake of ferric and ferrous iron. Am J Physiol, 279:G767–G774. 2000.
71.
ConstantineCC, AndersonGJ, VulpeCD, McLarenCE, BahloM, YeapHL, GertigDM, OsborneNJ, BertalliNA, BeckmanKB, ChenV, MatakP, McKieAT, DelatyckiMB, OlynykJK, EnglishDR, SoutheyMC, GilesGG, HopperJL, AllenKJ, GurrinLC. A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis. Br J Haematol, 147:140–149. 2009.
72.
CoopermanSS, Meyron-HoltzEG, Olivierre-WilsonH, GhoshMC, McConnellJP, RouaultTA. Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood, 106:1084–1091. 2005.
73.
CorradiniE, GarutiC, MontosiG, VenturaP, AndriopoulosBJr., LinHY, PietrangeloA, BabittJL. Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis. Gastroenterology, 137:1489–1497. 2009.
74.
CorradiniE, MeynardD, WuQ, ChenS, VenturaP, PietrangeloA, BabittJL. Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology, 54:273–284. 2011.
75.
CorsiB, CozziA, ArosioP, DrysdaleJ, SantambrogioP, CampanellaA, BiasiottoG, AlbertiniA, LeviS. Human mitochondrial ferritin expressed in HeLa cells incorporates iron and affects cellular iron metabolism. J Biol Chem, 277:22430–22437. 2002.
76.
CorwinHL. The role of erythropoietin therapy in the critically ill. Transfus Med Rev, 20:27–33. 2006.
77.
CourselaudB, PigeonC, InoueY, InoueJ, GonzalezFJ, LeroyerP, GilotD, BoudjemaK, Guguen-GuillouzoC, BrissotP, LoréalO, IlyinG. C/EBPα regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism. J Biol Chem, 277:41163–41170. 2002.
78.
CoxEV, MeynellMJ, NorthamBE, CookeWT. The anaemia of scurvy. Am J Med, 42:220–227. 1967.
79.
CoxTC, BawdenMI, MartinA, MayBK. Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron responsive element in the mRNA. EMBO J, 10:1891–1902. 1991.
80.
CraneFL, LöwH. NADH oxidation in liver and fat cell plasma membranes. FEBS Lett, 68:153–156. 1976.
81.
CravenCM, AlexanderJ, EldridgeM, KushnerJP, BernsteinS, KaplanJ. Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis. Proc Natl Acad Sci U S A, 84:3457–3461. 1987.
82.
DasslerK, ZydekM, WanzikK, KaupM, FuchsH. Release of the soluble transferrin receptor is directly regulated by binding of its ligand ferritransferrin. J Biol Chem, 281:3297–3304.
83.
De DomenicoI, McVey WardD, KaplanJ. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol, 9:72–81. 2008.
84.
De DomenicoI, WardDM, MusciG, KaplanJ. Iron overload due to mutations in ferroportin. Haematologica, 91:92–95. 2006.
85.
De DomenicoI, WardDM, NemethE, VaughnMB, MusciG, GanzT, KaplanJ. The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci U S A, 102:8955–8960. 2005.
86.
De DomenicoI, WardDM, MusciG, KaplanJ. Evidence for the multimeric structure of ferroportin. Blood, 109:2205–2209. 2007.
87.
De SilvaDM, AskwithCC, KaplanJ. Molecular mechanisms of iron uptake in eukaryotes. Physiol Rev, 76:31–47. 1996.
88.
DeaneR, ZhengW, ZlokovicBV. Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain. J Neurochem, 88:813–820. 2004.
89.
Del PrincipeD, AviglianoL, SaviniI, CataniMV. Trans-plasma membrane electron transport in mammals: Functional significance in health and disease. Antioxid Redox Signal, 14:2289–2318. 2011.
DoubleKL, MaywaldM, SchmittelM, RiedererP, GerlachM. In vitro studies of ferritin iron release and neurotoxicity. J Neurochem, 70:2492–2499. 1998.
93.
DringenR, BishopGM, KoeppeM, DangTN, RobinsonSR. The pivotal role of astrocytes in the metabolism of iron in the brain. Neurochem Res, 32:1884–1890. 2000.
94.
DringenR, BishopGM, KoeppeM, DangTN, RobinsonSR. The pivotal role of astrocytes in the metabolism of iron in the brain. Neurochem Res, 32:1884–1890. 2007.
95.
DrysdaleJ, ArosioP, InvernizziR, CazzolaM, VolzA, CorsiB, BiasiottoG, LeviS. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol Dis, 29:376–383. 2002.
96.
DuX, SheE, GelbartT, TruksaJ, LeeP, XiaY, KhovananthK, MuddS, MannN, MorescoEMY, BeutlerE, BeutlerB. The serine protease TMPRSS6 is required to sense iron deficiency. Science, 320:1088–1092. 2008.
97.
EasthamEJ, BellJI, DouglasAP. Iron-transport characteristics of vesicles of brush-border and basolateral plasma membrane from the rat enterocyte. Biochem J, 164:289–294. 1977.
98.
EnnsCA, SuomalainenHA, GebhardtJE, SchröderJ, SussmanHH. Human transferrin receptor: expression of the receptor is assigned to chromosome 3. Proc Natl Acad Sci U S A, 79:3241–3245. 1982.
99.
ErlandsenH, PatchMG, GamezA, StraubM, StevensRC. Structural studies on phenylalanine hydroxylase and implications toward understanding and treating phenylketonuria. Pediatrics, 112:1557–1565.
100.
EspositoBP, BreuerW, SirankaprachaP, PootrakulP, HershkoC, CabantchikZI. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood, 102:2670–2677. 2003.
101.
FaucheuxBA, NillesseN, DamierP, SpikG, Mouatt-PrigentA, PierceA, LeveugleB, KubisN, HauwJ-J, AgidY, HirschEC. Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease. Proc Natl Acad Sci U S A, 92:9603–9607. 1995.
102.
FederJN, PennyDM, IrrinkiA, LeeVK, LebrónJA, WatsonN, TsuchihashiZ, SigalE, BjorkmanPJ, SchatzmanRC. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci U S A, 95:1472–1477. 1998.
103.
FederJN, TsuchihashiZ, IrrinkiA, LeeVK, MapaFA, MorikangE, PrassCE, StarnesSM, WolffRK, ParkkilaS, SlyWS, SchatzmanRC. The hemochromatosis founder mutation in HLA-H disrupts β2-microglobulin interaction and cell surface expression. J Biol Chem, 272:14025–14028. 1997.
104.
FentonHJH. Oxidation of tartaric acid in presence of iron. J Chem Soc Trans, 65:899–910. 1894.
105.
FillebeenC, ChahineD, CaltagironeA, SegalP, PantopoulosK. A phosphomimetic mutation at Ser-138 renders iron regulatory protein 1 sensitive to iron-dependent degradation. Mol Cell Biol, 23:6973–6981. 2003.
106.
FillebeenC, DescampsL, DehouckM-P, FenartL, BenaïssaM, SpikG, CecchelliR, PierceA. Receptor-mediated transcytosis of lactoferrin through the blood–brain barrier. J Biol Chem, 274:7011–7017. 1999.
107.
FinbergKE, HeeneyMM, CampagnaDR, AydinokY, PearsonHA, HartmanKR, MayoMM, Samuel SM StrouseJJ, MarkianosK, AndrewsNC, FlemingMD. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)Nat Genet, 40:569–571. 2008.
108.
FinbergKE, WhittleseyRL, FlemingMD, AndrewsNC. Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis. Blood, 115:3817–3826. 2010.
109.
FinchC. Regulators of iron balance in humans. Blood, 84:1697–1702. 1994.
110.
FischbachFA, GregoryDW, HarrisonPM, HoyTG, WilliamsJM. On the structure of hemosiderin and its relationship to ferritin. J Ultrastruct Res, 37:495–503. 1971.
111.
FischbachMA, LinH, LiuDR, WalshCT. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat Chem Biol, 2:132–138. 2006.
112.
FlashmanE, DaviesSL, YeohKK, SchofieldCJ. Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. Biochem J, 427:135–142. 2010.
113.
FlemingMD, RomanoMA, SuMA, GarrickLM, GarrickMD, AndrewsNC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci U S A, 95:1148–1153. 1998.
114.
FlemingMD, Trenor IIICC, SuMA, FoernzlerD, BeierDR, DietrichWF, AndrewsNC. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene p383. Nat Genet, 16:383–386. 1997.
115.
FlemingPJ, KentUM. Cytochrome b561, ascorbic acid, and transmembrane electron transfer. Am J Clin Nutr, 54:1173S–1178S. 1991.
116.
FolguerasAR, de LaraFM, PendásAM, GarabayaC, RodríguezF, AstudilloA, BernalT, CabanillasR, López-OtínC, VelascoG. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood, 112:2539–2545. 2008.
117.
FootNJ, DaltonHE, Shearwin-WhyattLM, DorstynL, TanSS, YangB, KumarS. Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2. Blood, 112:4268–4275. 2008.
118.
ForejtnikovaH, VieillevoyeM, ZermatiY, LambertM, PellegrinoRM, GuihardS, GaudryM, CamaschellaC, LacombeC, RoettoA, MayeuxP, VerdierF. Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis. Blood, 116:5357–5367. 2010.
119.
FriedlichAL, TanziRE, RogersJT. The 5′-untranslated region of Parkinson's disease α-synuclein messenger RNA contains a predicted iron responsive element. Mol Psychiatry, 12:222–231. 2007.
120.
FujisawaH, OkunoS. Regulatory mechanism of tyrosine hydroxylase activity. Biochem Biophys Res Commun, 338:271–276. 2005.
121.
GanzT. Hepcidin and iron regulation, 10 years later. Blood, 117:4425–4433. 2011.
122.
GanzT. Molecular pathogenesis of anemia of chronic disease. Pediatr Blood Cancer, 46:554–557. 2006.
123.
GaoJ, ChenJ, De DomenicoI, KoellerDM, HardingCO, FlemingRE, KoeberlDD, EnnsCA. Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice. Blood, 115:3374–3381. 2010.
124.
GhioAJ, Nozik-GrayckE, TuriJ, JaspersI, MercatanteDR, KoleR, PiantadosiCA. Superoxide-dependent iron uptake. A new role for anion exchange protein 2. Am J Respir Cell Mol Biol, 29:653–660. 2003.
125.
GiannettiAM, BjörkmanPJ. HFE and transferrin directly compete for transferrin receptor in solution and at the cell surface. J Biol Chem, 279:25866–25875. 2004.
126.
GiannettiAM, SnowPM, ZakO, BjörkmanPJ. Mechanism for multiple ligand recognition by the human transferrin receptor. PLoS Biol, 1:341–350. 2003.
127.
GirijashankerK, HeL, SoleimaniM, ReedJM, LiH, LiuZ, WangB, DaltonTP, NebertDW. Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter. Mol Pharmacol, 73:1413–1423. 2008.
128.
GkouvatsosK, WagnerJ, PapanikolaouG, SebastianiG, PantopoulosK. Conditional disruption of mouse Hfe2 gene: Maintenance of systemic iron homeostasis requires hepatic but not skeletal muscle hemojuvelin. Hepatology, 54:1800–1807. 2011.
129.
GoswamiT, AndrewsNC. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem, 281:28494–28498. 2006.
GreenbergGR, WintrobeMM. A labile iron pool. J Biol Chem, 165:397–398. 1946.
134.
GroganG. Cytochromes P450: exploiting diversity and enabling application as biocatalysts. Curr Opin Chem Biol, 15:1–8. 2010.
135.
GrootveldM, BellJD, HalliwellB, AruomaOI, BomfordA, SadlerPJ. Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. J Biol Chem, 264:4417–4422. 1989.
136.
GrosG, WittenbergBA, JueT. Myoglobin's old and new clothes: from molecular structure to function in living cells. J Exp Biol, 213:2713–2725. 2010.
137.
GuillemF, LawsonS, KannengiesserC, WestermanM, BeaumontC, GrandchampB. Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiency. Blood, 112:2089–2091. 2008.
138.
GunshinH, AllersonCR, Polycarpou-SchwarzM, RoftsA, RogersJT, KishiF, HentzeMW, RouaultTA, AndrewsNC, HedigerMA. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett, 509:309–316. 2001.
139.
GunshinH, MackenzieB, BergerUV, GunshinY, RomeroMF, BoronWF, NussbergerS, GollanJL, HedigerMA. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature, 388:482–488. 1997.
140.
GunshinH, StarrCN, DirenzoC, FlemingMD, JinJ, GreerEL, SellersVM, GalicaSM, AndrewsNC. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood, 106:2879–2883. 2005.
141.
GuoB, PhillipsJD, YuY, LeiboldEA. Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem, 270:21645–21651. 1995.
142.
GutteridgeJM, SmithA. Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation. Biochem J, 256:861–865. 1988.
143.
HaasH, EisendleM, TurgeonBG. Siderophores in fungal physiology and virulence. Annu Rev Phytopathol, 46:149–187. 2008.
144.
HaaseVH. Hypoxic regulation of erythropoiesis and iron metabolism. Am J Physiol Renal Physiol, 299:F1–F13. 2010.
145.
HaberF, WeissJ. The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc London, Ser A, 147:332–351. 1934.
146.
HanO. Molecular mechanism of intestinal iron absorption. Metallomics, 3:103–109. 2011.
147.
HarrisonPM, ArosioP. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta, 1275:161–203. 1996.
148.
HellmanNE, GitlinJD. Ceruloplasmin metabolism and function. Annu Rev Nutr, 22:439–458. 2002.
149.
HentzeMW, KühnLC. 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, 93:8175–8182. 1996.
150.
HentzeMW, MuckenthalerMU, AndrewsNC. Balancing acts: molecular control of mammalian iron metabolism. Cell, 117:285–297. 2004.
151.
HentzeMW, MuckenthalerMU, GalyB, CamaschellaC. Two to tango: regulation of mammalian iron metabolism. Cell, 142:24–38. 2010.
HershkoC, GrahamG, BatesGW, RachmilewitzE. Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. BrJ Haematol, 40:255–263. 1978.
154.
HodgesVM, RaineyS, LappinTR, MaxwellAP. Pathophysiology of anemia and erythrocytosis. Crit Rev Oncol Hematol, 64:139–158. 2007.
155.
HögbomM. Metal use in ribonucleotide reductase R2, di-iron, di-manganese and heterodinuclear—an intricate bioinorganic workaround to use different metals for the same reaction. Metallomics, 3:110–120. 2011.
156.
HorowitzMP, GreenamyreJT. Mitochondrial iron metabolism and its role in neurodegeneration. J Alzheimer's Dis, 20,Suppl 2:S551–S568. 2010.
157.
HrkalZ, VodrážkaZ, KalousekI. Transfer of heme from ferrihemoglobin and ferrihemoglobin isolated chains to hemopexin. Eur J Biochem, 43:73–78. 1974.
158.
HuangFW, PinkusJL, PinkusGS, FlemingMD, AndrewsNC. A mouse model of juvenile hemochromatosis. J Clin Invest, 115:2187–2191. 2005.
159.
HuangML-H, LaneDJR, RichardsonDR. Mitochondrial mayhem: the mitochondrion as a modulator of iron metabolism and its role in disease. Antioxid Redox Signal, 15:3003–3019. 2011.
160.
HubertN, HentzeMW. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc Natl Acad Sci U S A, 99:12345–12350. 2002.
161.
HuebersHA, BeguinY, PootrakulP, EinspahrD, FinchCA. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood, 75:102–107. 1990.
162.
HuntS, GreenJ, ArtymiukPJ. Hemolysin E (HlyE, ClyA, SheA) and related toxins. Adv Exp Med Biol, 677:116–126. 2010.
163.
HvidbergV, ManieckiMB, JacobsenC, HøjrupP, MøllerHJ, MoestrupSK. Identification of the receptor scavenging hemopexin-heme complexes. Blood, 106:2572–2579. 2005.
164.
InmanRS, Wessling-ResnickM. Characterization of transferrin-independent iron transport in K562 cells. Unique properties provide evidence for multiple pathways of iron uptake. J Biol Chem, 268:8521–8528. 1993.
165.
IshikawaH, KatoM, HoriH, IshimoriK, KirisakoT, TokunagaF, IwaiK. Involvement of heme regulatory motif in heme-mediated ubiquitination and degradation of IRP2. Mol Cell, 19:171–181. 2005.
166.
IvanM, KondoK, YangH, KimW, ValiandoJ, OhhM, SalicA, AsaraJM, LaneWS, KaelinWGJr.HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science, 292:464–468. 2001.
IwaiK, KlausnerRD, RouaultTA. Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. EMBO J, 14:5350–5357. 1995.
169.
JaakkolaP, MoleDR, TianY-M, WilsonMI, GielbertJ, GaskellSJ, KriegsheimA, HebestreitHF, MukherjiM, SchofieldCJ, MaxwellPH, PughCW, RatcliffePJ. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292:468–472. 2001.
170.
JacobsA. Low-molecular weight intracellular iron transport compounds. Blood, 50:433–439. 1977.
171.
JacolotS, FérecC, MuraC. Iron responses in hepatic, intestinal and macrophage/monocyte cell lines under different culture conditions. Blood Cells Mol Dis, 41:100–108. 2008.
172.
JeongJ, GuerinotML. Homing in on iron homeostasis in plants. Trends Plant Sci, 14:280–285. 2009.
173.
JeongJ, RouaultTA, LevineRL. Identification of a heme-sensing domain in iron regulatory protein 2. J Biol Chem, 279:45450–45454. 2004.
174.
JingSQ, TrowbridgeIS. Identification of the intermolecular disulfide bonds of the human transferrin receptor and its lipid-attachment site. EMBO J, 6:327–331. 1987.
JohnsonMB, ChenJ, MurchisonN, GreenFA, EnnsCA. Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway. Mol Biol Cell, 18:743–754. 2007.
177.
JordanI, KaplanJ. The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity. Biochem J, 302:875–879. 1994.
178.
KahnSB, BrodskyI. Vitamin B12, ascorbic acid and iron metabolism in scurvy. Am J Med, 40:119–126. 1966.
179.
KakarS, HoffmanFG, StorzJF, FabianM, HargroveMS. Structure and reactivity of hexacoordinate hemoglobins. Biophys Chem, 152:1–14. 2010.
180.
KakhlonO, CabantchikZI. The labile iron pool: characterization, measurement, and participation in cellular processes. Free Radic Biol Med, 33:1037–1046. 2002.
181.
KarinM, MintzB. Receptor-mediated endocytosis of transferrin in developmentally totipotent mouse teratocarcinoma stem cells. J Biol Chem, 256:3245–3252. 1981.
182.
KautzL, Besson-FournierC, MeynardD, LatourC, RothM-P, CoppinH. Iron overload induces BMP6 expression in the liver but not in the duodenum. Haematologica, 96:199–203. 2011.
183.
KautzL, MeynardD, Besson-FournierC, DarnaudV, Al SaatiT, CoppinH, RothM-P. BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression. Blood, 114:2515–2520. 2009.
184.
KawabataH, GermainRS, VuongPT, NakamakiT, SaidJW, KoefflerHP. Transferrin receptor 2-α supports cell growth both in iron-chelated cultured cells and in vivo. J Biol Chem, 275:16618–16625. 2000.
185.
KawabataH, YangR, HiramaT, VuongPT, KawanoS, GombartAF, KoefflerHP. Molecular cloning of transferrin receptor 2: A new member of the transferrin receptor-like family. J Biol Chem, 274:20826–20832. 1999.
186.
KeY, WuJ, LeiboldEA, WaldenWE, TheilEC. Loops and bulge/loops in iron-responsive element isoforms influence iron regulatory protein binding. Fine-tuning of mRNA regulation?J Biol Chem, 273:23637–23640. 1998.
187.
KemnaEHJM, TjalsmaH, PodustVN, SwinkelsDW. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem, 53:620–628. 2007.
188.
This reference has been deleted.
189.
KirkmanHN, GaetaniGF. Mammalian catalase: a venerable enzyme with new mysteries. Trends Biochem Sci, 32:44–50. 2007.
190.
KnutsonMD. Iron-sensing proteins that regulate hepcidin and enteric iron absorption. Annu Rev Nutr, 30:149–171. 2010.
191.
KnutsonMD, VafaMR, HaileDJ, Wessling-ResnickM. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood, 102:4191–4197. 2003.
192.
KohlerSA, HendersonBR, KühnLC. Succinate dehydrogenase B mRNA of Drosophila melanogaster has a functional iron-responsive element in its 5′-untranslated region. J Biol Chem, 270:30781–30786. 1995.
193.
KohlerSA, MenottiE, KühnLC. Molecular cloning of mouse glycolate oxidase. High evolutionary conservation and presence of an iron-responsive element-like sequence in the mRNA. J Biol Chem, 274:2401–2407. 1999.
194.
KolbergM, StrandKR, GraffP, AnderssonKK. Structure, function, and mechanism of ribonucleotide reductases. Biochim Biophys Acta, 1699:1–34. 2004.
195.
KönigsbergerL-C, KönigsbergerE, MayPM, HefterGT. Complexation of iron(III) and iron(II) by citrate. Implications for iron speciation in blood plasma. J Inorg Biochem, 78:175–184. 2000.
196.
KonijnAM, GlicksteinH, VaismanB, Meyron-HoltzEG, SlotkiIN, CabantchikZI. The cellular labile iron pool and intracellular ferritin in K562 cells. Blood, 94:2128–2134. 1999.
197.
KoortsAM, LevayPF, HallAN, van der MerweCF, BeckerPJ, ViljoenM. Expression of the H-subunit and L-subunit of ferritin in bone marrow macrophages and cells of the erythron during cellular immune activation. Blood Cells Mol Dis, 47:50–55. 2011.
198.
KouryMJ, PonkaP. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr, 24:105–131. 2004
199.
KrauseA, NeitzS, MägertH-J, SchulzA, ForssmannWG, Schulz-KnappeP, AdermannK. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett, 480:147–150. 2000.
200.
KruszewskiM. The role of labile iron pool in cardiovascular diseases. Acta Biochim Polon, 51:471–480. 2004.
201.
KulaksizH, TheiligF, BachmannS, GehrkeSG, RostD, JanetzkoA, CetinY, StremmelW. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. J Endocrinol, 184:361–370. 2005.
202.
KurzT, EatonJW, BrunkUT. The role of lysosomes in iron metabolism and recycling. Int J Biochem Cell Biol, 43:1686–1697. 2011.
203.
LakhalS, SchödelJ, TownsendARM, PughCW, RatcliffePJ, MoleDR. Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis. J Biol Chem, 286:4090–4097. 2011.
204.
LaneDJR, LawenA. Non-transferrin iron reduction and uptake are regulated by transmembrane ascorbate cycling in K562 cells. J Biol Chem, 283:12701–12708. 2008.
205.
LaneDJ, LawenA. Ascorbate and plasma membrane electron transport—enzymes vs efflux. Free Radic Biol Med, 47:485–495. 2009.
206.
LaneDJR, LawenA. Transplasma membrane electron transport comes in two flavors. BioFactors, 34:191–200. 2009.
207.
LaneDJR, RobinsonSR, CzerwinskaH, BishopGM, LawenA. Two routes of iron accumulation in astrocytes: ascorbate-dependent ferrous iron uptake via the divalent metal transporter (DMT1) plus an independent route for ferric iron. Biochem J, 432:123–132. 2010.
208.
LangeH, KispalG, LillR. Mechanism of iron transport to the site of heme synthesis inside yeast mitochondria. J Biol Chem, 274:18989–18996. 1999.
LarsenR, GozzelinoR, JeneyV, TokajiL, BozzaFA, JapiassúAM, BonaparteD, CavalcanteMM, ChoraA, FerreiraA, MargutiI, CardosoS, SepúlvedaN, SmithA, SoaresMP. A central role for free heme in the pathogenesis of severe sepsis. Sci Transl Med, 2:51ra71. 2010.
211.
Latunde-DadaGO, SimpsonRJ, McKieAT. Duodenal cytochrome B expression stimulates iron uptake by human intestinal epithelial cells. J Nutr, 138:991–995. 2008.
212.
Latunde-DadaGO, Van der WesthuizenJ, VulpeCD, AndersonGJ, SimpsonRJ, McKieAT. Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism. Blood Cells Mol Dis, 29:356–360. 2002.
213.
Latunde-DadaGO, XiangL, SimpsonRJ, McKieAT. Duodenal cytochrome b (Cybrd 1) and HIF-2α expression during acute hypoxic exposure in mice. Eur J Nutr, 50:699–704. 2011.
214.
LaVauteT, SmithS, CoopermanS, IwaiK, LandW, Meyron-HoltzE, DrakeSK, MillerG, Abu-AsabM, TsokosM, Switzer RIII, GrinbergA, LoveP, TresserN, RouaultTA. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet, 27:209–214. 2001.
215.
LawrenceCM, RayS, BabyonyshevM, GalluserR, BorhaniDW, HarrisonSC. Crystal structure of the ectodomain of human transferrin receptor. Science, 286:779–782. 1999.
216.
LayerG, JahnD, JahnM. Heme biosynthesis. Handbook of Porphyrin Science with Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medicine, 15KadishKM, SmithKM, GuilardR., HacksackNJ. London, Singapore: World Scientific Publishing Co. Pte. Ltd., 2011; 159–215.
217.
LeeD-H, ZhouL-J, ZhouZ, XieJ-X, JungJ-U, LiuY, XiC-X, MeiL, XiongW-C. Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis. Blood, 115:3136–3145. 2010.
218.
LeeFS, PercyMJ. The HIF pathway and erythrocytosis. Annu Rev Pathol, 6:165–192. 2011.
219.
LeeP, PengH, GelbartT, BeutlerE. The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and β2-microglobulin-deficient hepatocytes. Proc Natl Acad Sci U S A, 101:9263–9265. 2004.
220.
LeimbergMJ, PrusE, KonijnAM, FibachE. Macrophages function as a ferritin iron source for cultured human erythroid precursors. J Cell Biochem, 103:1211–1218. 2008.
221.
LenoirA, DescheminJ-C, KautzL, RamsayAJ, RothM-P, Lopez-OtinC, VaulontS, NicolasG. Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6. Blood, 117:647–650. 2011.
222.
Lesbordes-BrionJ-C, ViatteL, BennounM, LouD-Q, RameyG, HoubronC, HamardG, KahnA, VaulontS. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood, 108:1402–1405. 2006.
223.
LesnikovV, GordenN, FaustoN, SpauldingE, CampbellJ, ShulmanH, FlemingRE, DeegHJ. Transferrin fails to provide protection against Fas-induced hepatic injury in mice with deletion of functional transferrin-receptor type 2. Apoptosis, 13:1005–1012. 2008.
224.
LeviS, CorsiB, BosisioM, InvernizziR, VolzA, SanfordD, ArosioP, DrysdaleJ. A human mitochondrial ferritin encoded by an intronless gene. J Biol Chem, 276:24437–24440. 2001.
225.
LevyJE, JinO, FujiwaraY, KuoF, AndrewsNC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet, 21:396–399. 1999.
LiZ, LaiZ, YaK, FangD, HoYW, LeiY, MingQZ. Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells. J Cell Mol Med, 12:569–579. 2008.
LinL, GoldbergYP, GanzT. Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood, 106:2884–2889. 2005.
230.
LiuzziJP, AydemirF, NamH, KnutsonMD, CousinsRJ. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci U S A, 103:13612–13617. 2006.
231.
LoenarzC, SchofieldCJ. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol, 4:152–156. 2008.
232.
LokCN, PonkaP. Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem, 274:24147–24152. 1999.
233.
LudwiczekS, AignerE, TheurlI, WeissG. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood, 101:4148–4154. 2003.
234.
LyJD, LawenA. Transplasma membrane electron transport: enzymes involved and biological function. Redox Rep, 8:3–21. 2003.
235.
LynchRE. Fridovich I Permeation of the erythrocyte stroma by superoxide radical. J Biol Chem, 253:4697–4699. 1978.
236.
MaY, YehM, YehKY, GlassJ. Iron Imports. V. Transport of iron through the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol, 290:G417–G422. 2006.
237.
MackenzieB, UjwalML, ChangM-H, RomeroMF, HedigerMA. Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and uncoupled fluxes. Pflügers Arch Eur J Physiol, 451:544–558. 2006.
238.
MagroG, CataldoI, AmicoP, TorrisiA, VecchioGM, ParentiR, AsioliS, RecuperoD, D'AgataV, MucignatMT, PerrisR. Aberrant expression of TfR1/CD71 in thyroid carcinomas identifies a novel potential diagnostic marker and therapeutic target. Thyroid, 21:267–277. 2011.
239.
MakinoM, SawaiH, ShiroY, SugimotoH. Crystal structure of the carbon monoxide complex of human cytoglobin. Proteins, 79:1143–1153. 2011.
240.
MaleckiEA, DevenyiAG, BeardJL, ConnorJR. Existing, emerging mechanisms for transport of iron, manganese to the brain. J Neurosci Res, 56:113–122. 1999.
241.
MarshanskyV, FutaiM. The V-type H+-ATPase in vesicular trafficking: targeting, regulation and function. Curr Opin Cell Biol, 20:415–426. 2008.
242.
MastrogiannakiM, MatakP, KeithB, SimonMC, VaulontS, PeyssonnauxC. HIF-2α, but not HIF-1α, promotes iron absorption in mice. J Clin Invest, 119:1159–1166. 2009.
243.
MatthesS, MosienkoV, BashammakhS, AleninaN, BaderM. Tryptophan hydroxylase as novel target for the treatment of depressive disorders. Pharmacology, 85:95–109. 2010.
244.
MaukMR, SmithA, MaukAG. An alternative view of the proposed alternative activities of hemopexin. Protein Sci, 20:791–805. 2011.
245.
MaxwellPH, WiesenerMS, ChangGW, CliffordSC, VauxEC, CockmanME, WykoffCC, PughCW, MaherER, RatcliffePJ. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 399:271–275. 1999.
246.
MayJM, QuZc, MendirattaS. Role of ascorbic acid in transferrin-independent reduction and uptake of iron by U-937 cells. Biochem Pharmacol, 57:1275–1282. 1999.
247.
McKieAT, MarcianiP, RolfsA, BrennanK, WehrK, BarrowD, MiretS, BomfordA, PetersTJ, FarzanehF, HedigerMA, HentzeMW, SimpsonRJ. A novel duodenal iron regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell, 5:299–309. 2000.
248.
McKieAT, BarrowD, Latunde-DadaGO, RolfsA, SagerG, MudalyE, MudalyM, RichardsonC, BarlowD, BomfordA, PetersTJ, RajaKB, ShiraliS, HedigerMA, FarzanehF, SimpsonRJ. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science, 291:1755–1759. 2001.
249.
MelisMA, CauM, CongiuR, SoleG, BarellaS, CaoA, WestermanM, CazzolaM, GalanelloR. A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. Haematologica, 93:1473–1479. 2008.
250.
MerleU, FeinE, GehrkeSG, StremmelW, KulaksizH. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology, 148:2663–2668. 2007.
251.
MetzJ. A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull, 29:S74–S85. 2008.
252.
MeynardD, KautzL, DarnaudV, Canonne-HergauxF, CoppinH, RothM-P. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet, 41:478–481. 2009.
253.
Meyron-HoltzEG, GhoshMC, RouaultTA. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science, 306:2087–2090. 2004.
254.
Meyron-HoltzEG, GhoshMC, IwaiK, LaVauteT, BrazzolottoX, BergerUV, LandW, Ollivierre-WilsonH, GrinbergA, LoveP, RouaultTA. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J, 23:386–395. 2004.
MiletJ, Le GacG, ScotetV, GourlaouenI, ThèzeC, MosserJ, BourgainC, DeugnierY, FérecC. A common SNP near BMP2 is associated with severity of the iron burden in HFE p.C282Y homozygous patients: a follow-up study. Blood Cells Mol Dis, 44:34–37. 2010.
257.
MilmanN. Anemia—still a major health problem in many parts of the world!Ann Hematol, 90:369–377. 2011.
258.
MizutaniA, SanukiR, KakimotoK, KojoS, TaketaniS. Involvement of 101F6, a homologue of cytochrome b561, in the reduction of ferric ions. J Biochem, 142:699–705. 2007.
259.
MoleDR. Iron homeostasis and its interaction with prolyl hydroxylases. Antioxid Redox Signal, 12:445–458. 2010.
260.
MoosT. Immunohistochemical localization of intraneuronal transferrin receptor immunoreactivity in the adult mouse central nervous system. J Comp Neurol, 375:675–692. 1996.
261.
MoosT, MorganEH. Transferrin and transferrin receptor function in brain barrier systems. Cell Mol Neurobiol, 20:77–95. 2000.
262.
MoosT, MorganEH. A morphological study of the developmentally regulated transport of iron into the brain. Dev Neurosci, 24:99–105. 2002.
263.
MoosT, NielsenTR, SkjørringeT, MorganEH. Iron trafficking inside the brain. J Neurochem, 103:1730–1740. 2007.
264.
MorganEH. Transferrin, biochemistry, physiology and clinical significance. Molec Asp Med, 4:1–123. 1981.
265.
MorganEH. Mechanisms of iron transport into rat erythroid cells. J Cell Physiol, 186:193–200. 2001.
266.
MorooI, UjiieM, WalkerBL, TiongJWC, VitalisTZ, KarkanD, GabathulerR, MoiseAR, JefferiesWA. Identification of a novel route of iron transcytosis across the mammalian blood–brain barrier. Microcirculation, 10:457–462. 2003.
267.
MuckenthalerMU, GalyB, HentzeMW. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr, 28:197–213. 2008.
268.
MukhopadhyayCK, MazumderB, FoxPL. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency. J Biol Chem, 275:21048–21054. 2000.
269.
MüllnerEW, KühnLC. A stem–loop in the 3′ untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm. Cell, 53:815–825. 1988.
270.
MuñozM, García-ErceJA, RemachaAF. Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis. J Clin Pathol, 64:281–286. 2011.
271.
MusílkováJ, KriegerbeckováK, KrùsekJ, KovárJ. Specific binding to plasma membrane is the first step in the uptake of nontransferrin iron by cultured cells. Biochim Biophys Acta, 1369:103–108. 1998.
272.
NairzM, WeissG. Molecular and clinical aspects of iron homeostasis: From anemia to hemochromatosis. Wien Klin Wochenschr, 118:442–462. 2006.
273.
NeckersLM, CossmanJ. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A, 80:3494–3498. 1983.
274.
NemethE, RiveraS, GabayanV, KellerC, TaudorfS, PedersenBK, GanzT. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest, 113:1271–1276. 2004.
275.
NemethE, TuttleMS, PowelsonJ, VaughnMB, DonovanA, WardDM, GanzT, KaplanJ. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science, 306:2090–2093. 2004.
276.
NicolasG, BennounM, DevauxI, BeaumontC, GrandchampB, KahnA, VaulontS. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A, 98:8780–8785. 2001.
277.
NicolasG, ChauvetC, ViatteL, DananJL, BigardX, DevauxI, BeaumontC, KahnA, VaulontS. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest, 110:1037–1044. 2002.
278.
NiederkoflerV, SalieR, ArberS. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest, 115:2180–2186. 2005.
NúñezM-T, GaeteV, WatkinsJA, GlassJ. Mobilization of iron from endocytic vesicles. The effects of acidification and reduction. J Biol Chem, 265:6688–6692. 1990.
281.
NytkoKJ, MaedaN, SchläfliP, SpielmannP, WengerRH, StiehlDP. Vitamin C is dispensable for oxygen sensing in vivo. Blood, 117:5485–5493. 2011.
282.
O'ConnellM, HalliwellB, MoorhouseCP, AruomaOI, BaumH, PetersTJ. Formation of hydroxyl radicals in the presence of ferritin and haemosiderin. Is haemosiderin formation a biological protective mechanism?Biochem J, 234:727–731. 1986.
283.
OctaveJ-N, SchneiderY-J, HoffmannP, TrouetA, CrichtonRR. Transferrin protein and iron uptake by cultured rat fibroblasts. FEBS Lett, 108:127–130. 1979.
284.
OhgamiRS, CampagnaDR, GreerEL, AntiochosB, McDonaldA, ChenJ, SharpJJ, FujiwaraY, BarkerJE, FlemingMD. Identification of a ferrireductase required for efficient transferrin dependent iron uptake in erythroid cells. Nat Genet, 37:1264–1269. 2005.
285.
OzerA, BruickRK. Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?Nat Chem Biol, 3:144–153. 2007.
286.
PantopoulosK. Function of the hemochromatosis protein HFE: lessons from animal models. World J Gastroenterol, 14:6893–6901. 2008.
287.
PapanikolaouG, SamuelsME, LudwigEH, MacDonaldMIE, FranchiniPL, DubéM-P, AndresL, MacFarlaneJ, SakellaropoulosN, PolitouM, NemethE, ThompsonJ, RislerJK, ZaborowskaC, BabakaiffR, RadomskiCC, PapeTD, DavidasO, ChristakisJ, BrissotP, LockitchG, GanzT, HaydenMR, GoldbergYP. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet, 36:77–82. 2004.
288.
PappalardiMB, McNultyDE, MartinJD, FisherKE, JiangY, BurnsMC, ZhaoH, HoT, SweitzerS, SchwartzB, AnnanRS, CopelandRA, TumminoPJ, LuoL. Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites. Biochem J, 436:363–369. 2011.
289.
ParkCH, ValoreEV, WaringAJ, GanzT. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem, 276:7806–7810. 2001.
290.
PelizzoniI, ZacchettiD, SmithCP, GrohovazF, CodazziF. Expression of divalent metal transporter 1 in primary hippocampal neurons: reconsidering its role in non-transferrin-bound iron influx. J Neurochem, 120:269–278. 2012.
291.
PeslovaG, PetrakJ, KuzelovaK, HrdyI, HaladaP, KuchelPW, Soe-LinS, PonkaP, SutakR, BeckerE, HuangML-H, RahmantoYS, RichardsonDR, VyoralD. Hepcidin, the hormone of iron metabolism, is bound specifically to α-2-macroglobulin in blood. Blood, 113:6225–6236. 2009.
292.
PeyssonnauxC, ZinkernagelAS, SchuepbachRA, RankinE, VaulontS, HaaseVH, NizetV, JohnsonRS. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)J Clin Invest, 117:1926–1932. 2007.
293.
PietrangeloA. Hepcidin in human iron disorders: therapeutic implications. J Hepatol, 54:173–181. 2011.
294.
PigeonC, IlyinG, CourselaudB, LeroyerP, TurlinB, BrissotP, LoréalO. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem, 276:7811–7819. 2001.
295.
Pinilla-TenasJJ, SparkmanBK, ShawkiA, IllingAC, MitchellCJ, ZhaoN, LiuzziJP, CousinsRJ, KnutsonMD, MackenzieB. Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. Am J Physiol Cell Physiol, 301:C862–C871. 2011.
296.
PipernoA, MarianiR, TrombiniP, GirelliD. Hepcidin modulation in human diseases: from research to clinic. World J Gastroenterol, 15:538–551. 2009.
297.
PitulaJS, DeckKM, ClarkeSL, AndersonSA, VasanthakumarA, EisensteinRS. Selective inhibition of the citrate-to-isocitrate reaction of cytosolic aconitase by phosphomimetic mutation of serine-711. Proc Natl Acad Sci U S A, 101:10907–10912. 2004.
298.
PoliM, LuscietiS, GandiniV, MaccarinelliF, FinazziD, SilvestriL, RoettoA, ArosioP. Transferrin receptor 2 and HFE regulate furin expression via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) signaling. Implications for transferrin-dependent hepcidin regulation. Haematologica, 95:1832–1840. 2010.
299.
PollaBS. Therapy by taking away: the case of iron. Biochem Pharmacol, 57:1345–1349. 1999.
QianZ-M, WuXM, FanM, YangL, DuF, YungW-H, KeY. Divalent metal transporter 1 is a hypoxia-inducible gene. J Cell Physiol, 226:1596–1603. 2001.
302.
QiuA, JansenM, SakarisA, MinSH, ChattopadhyayS, TsaiE, SandovalC, ZhaoR, AkabasMH, GoldmanID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell, 127:917–928. 2006.
303.
RaffinSB, WooCH, RoostKT, PriceDC, SchmidR. Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase. J Clin Invest, 54:1344–1352. 1974.
304.
RajpathakSN, CrandallJP, Wylie-RosettJ, KabatGC, RohanTE, HuFB. The role of iron in type 2 diabetes in humans. Biochim Biophys Acta, 1790:671–681. 2009.
305.
RameyG, DescheminJC, VaulontS. Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes. Haematologica, 94:765–772. 2009.
306.
RamosE, KautzL, RodriguezR, HansenM, GabayanV, GinzburgY, RothM-P, NemethE, GanzT. Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice. Hepatology, 53:1333–1341. 2011.
307.
ReardonTF, AllenDG. Time to fatigue is increased in mouse muscle at 37°C; the role of iron and reactive oxygen species. J Physiol, 587:4705–4716. 2009.
308.
RecalcatiS, MinottiG, CairoG. Iron regulatory proteins: from molecular mechanisms to drug development. Antioxid Redox Signal, 13:1593–1616. 2010.
309.
RhodesSL, RitzB. Genetics of iron regulation and the possible role of iron in Parkinson's disease. Neurobiol Dis, 32:183–195. 2008.
310.
RichardsonDR, MorganEH. The transferrin homologue, melanotransferrin (p97), is rapidly catabolized by the liver of the rat and does not effectively donate iron to the brain. Biochim Biophys Acta, 1690:124–133. 2004.
311.
RichardsonDR, KalinowskiDS, LauS, JanssonPJ, LovejoyDB. Cancer cell iron metabolism and the development of potent iron chelators as anti-tumour agents. Biochim Biophys Acta, 1790:702–717. 2009.
312.
RichardsonDR, LaneDJR, BeckerEM, HuangML, WhitnallM, Suryo RahmantoY, SheftelAD, PonkaP. Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol. Proc Natl Acad Sci U S A, 107:10775–10782. 2010.
313.
RobbA, Wessling-ResnickM. Regulation of transferrin receptor 2 protein levels by transferrin. Blood, 104:4294–4299. 2004.
314.
RochetteJ, Le GacG, LassouedK, FérecC, RobsonKJ. Factors influencing disease phenotype and penetrance in HFE haemochromatosis. Hum Genet, 128:233–248. 2010.
315.
RoettoA, TotaroA, CazzolaM, CicilanoM, BosioS, D'AscolaG, CarellaM, ZelanteL, KellyAL, CoxTM, GaspariniP, CamaschellaC. Juvenile hemochromatosis locus maps to chromosome 1q. Am J Hum Genet, 64:1388–1393. 1999.
316.
RolfsA, KvietikovaI, GassmannM, WengerRH. Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J Biol Chem, 272:20055–20062. 1997.
RothJA, SingletonS, FengJ, GarrickM, ParadkarPN. Parkin regulates metal transport via proteasomal degradation of the 1B isoforms of divalent metal transporter 1. J Neurochem, 113:454–464. 2010.
319.
RouaultTA, CoopermanS. Brain iron metabolism. Semin Pediatr Neurol, 13:142–148. 2006.
320.
RouaultTA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol, 2:406–414. 2006.
321.
RoyCN, EnnsCA. Iron homeostasis: new tales from the crypt. Blood, 96:4020–4027. 2000.
322.
RyanJD, RyanE, FabreA, LawlessMW, CroweJ. Defective bone morphogenic protein signaling underlies hepcidin deficiency in HFE hereditary hemochromatosis. Hepatology, 52:1266–1273. 2010.
323.
SahaR, SahaN, DonofrioRS, BesterveltLL. Microbial siderophores: a mini review. J Basic Microbiol, 2012[Epub ahead of print]DOI:10.1002/jobm.201100552.
324.
SalahudeenAA, ThompsonJW, RuizJC, MaH-W, KinchLN, LiQ, GrishinNV, BruickRK. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science, 326:722–726. 2009.
325.
SammarcoMC, DitchS, BanerjeeA, GrabczykE. Ferritin L and H subunits are differentially regulated on a post-transcriptional level. J Biol Chem, 283:4578–4587. 2008.
326.
SanchezM, GalyB, DandekarT, BengertP, VainshteinY, StollteJ, MuckenthalerMU, HentzeMW. Iron regulation and the cell cycle: Identification of an iron-responsive element in the 3′ untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategy. J Biol Chem, 281:22865–22874. 2006.
327.
SanchezM, GalyB, MuckenthalerMU, HentzeMW. Iron-regulatory proteins limit hypoxia-inducible factor-2α expression in iron deficiency. Nat Struct Mol Biol, 14:420–426. 2007.
328.
SchalinskeKL, ChenOS, EisensteinRS. Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization. J Biol Chem, 273:3740–3746. 1998.
329.
SchalkIJ, HannauerM, BraudA. New roles for bacterial siderophores in metal transport and tolerance. Environ Microbiol, 13:2844–2854. 2011.
330.
ScheersNM, SandbergA-S. Ascorbic acid uptake affects ferritin, Dcytb and Nramp2 expression in Caco-2 cells. Eur J Nutr, 47:401–408. 2008.
331.
SchmidtPJ, ToranPT, GiannettiAM, BjorkmanPJ, AndrewsNC. The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression. Cell Metab, 7:205–214. 2008.
332.
SekyereEO, DunnLL, RahmantoYS, RichardsonDR. Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in vivo. Blood, 107:2599–2601. 2006.
333.
ShahYM, MatsubaraT, ItoS, YimSH, GonzalezFJ. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab, 9:152–164. 2009.
334.
ShaneB. Folate and vitamin B12 metabolism: overview and interaction with riboflavin, vitamin B6, and polymorphisms. Food Nutr Bull, 29:S5–S16. 2008.
SheftelAD, LillR. The power plant of the cell is also a smithy: the emerging role of mitochondria in cellular iron homeostasis. Ann Med, 41:82–99. 2009.
338.
SheftelAD, KimSF, PonkaP. Non-heme induction of heme oxygenase-1 does not alter cellular iron metabolism. J Biol Chem, 282:10480–10486. 2007.
339.
SheftelA, StehlingO, LillR. Iron-sulfur proteins in health and disease. Trends Endocrinol Metab, 21:302–314. 2010.
340.
SheftelAD, ZhangAS, BrownC, ShirihaiOS, PonkaP. Direct interorganellar transfer of iron from endosome to mitochondrion. Blood, 110:125–132. 2007.
341.
ShiH, BenczeKZ, StemmlerTL, PhilpottCC. A cytosolic iron chaperone that delivers iron to ferritin. Science, 320:1207–1210.
342.
ShiY, MassagueJ. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell, 113:685–700. 2003.
343.
ShihYJ, BaynesRD, HudsonBG, FlowersCH, SkikneBS, CookJD. Serum transferrin receptor is a truncated form of tissue receptor. J Biol Chem, 265:19077–19081. 1990.
344.
ShvartsmanM, KikkeriR, ShanzerA, CabantchikZI. Non-transferrin-bound iron reaches mitochondria by a chelator-inaccessible mechanism: biological and clinical implications. Am J Physiol Cell Physiol, 293:C1383–C1394. 2007.
345.
SiddiqueA, KowdleyKV. Review article: the iron overload syndromes. Aliment Pharmacol Ther, 35:876–893. 2012.
346.
SilvestriL, PaganiA, CamaschellaC. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood, 111:924–931. 2008.
347.
SilvestriL, PaganiA, FaziC, GerardiG, LeviS, ArosioP, CamaschellaC. Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis. Blood, 109:4503–4510. 2007.
348.
SilvestriL, PaganiA, NaiA, De DomenicoI, KaplanJ, CamaschellaC. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab, 8:502–511. 2008.
349.
SimpsonRJ, McKieAT. Regulation of intestinal iron absorption: the mucosa takes control?Cell Metab, 10:84–87. 2009.
350.
SinghAK, SinghN, SinhaM, BhushanA, KaurP, SrinivasanA, SharmaS, SinghTP. Binding modes of aromatic ligands to mammalian heme peroxidases with associated functional implications: crystal structures of lactoperoxidase complexes with acetylsalicylic acid, salicylhydroxamic acid, and benzylhydroxamic acid. J Biol Chem, 284:20311–20318. 2009.
351.
SkaarEP. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog, 6:e1000949. 2010.
352.
SkikneBS, FlowersCH, CookJD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood, 75:1870–1876. 1990.
353.
SkikneBS, PunnonenK, CaldronPH, BennettMT, RehuM, GasiorGH, ChamberlinJS, SullivanLA, BrayKR, SouthwickPC. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am J Hematol, 86:923–927. 2011.
354.
SmithA. Links between cell-surface events involving redox-active copper and gene regulation in the hemopexin heme transport system. Antioxid Redox Signal, 2:157–175. 2000.
355.
SmithA. Mechanisms of cytoprotection by hemopexin. Handbook of Porphyrin Science with Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medicine, 15KadishKM, SmithKM, GuilardR., HacksackNJ. London: Singapore: World Scientific Publishing Co. Pte. Ltd., 2011; 217–355.
356.
SmithA, HuntRC. Hemopexin joins transferrin as representative members of a distinct class of receptor-mediated endocytic transport systems. Eur J Cell Biol, 53:234–245. 1990.
357.
SmithA, MorganWT. Haem transport to the liver by haemopexin. Receptor-mediated uptake with recycling of the protein. Biochem J, 182:47–54. 1979.
358.
SmithA, MorganWT. Transport of heme by hemopexin to the liver: evidence for receptor-mediated uptake. Biochem Biophys Res Commun, 84:151–157. 1978.
359.
SmithSR, CoopermanS, LavauteT, TresserN, GhoshM, Meyron-HoltzE, LandW, OllivierreH, JortnerB, Switzer RIII, MessingA, RouaultTA. Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Ann N Y Acad Sci, 1012:65–83. 2004.
360.
Soe-LinS, ApteSS, AndriopoulosBJr., AndrewsMC, SchranzhoferM, KahawitaT, Garcia-SantosD, PonkaP. Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc Natl Acad Sci U S A, 106:5960–5965. 2009.
361.
Soe-LinS, ApteSS, MikhaelMR, KayembeLK, NieG, PonkaP. Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling. Exp Hematol, 38:609–617. 2010.
362.
SongL, HobaughMR, ShustakC, CheleyS, BayleyH, GouauxJE. Structure of Staphyloccal α-hemolysin, a heptameric transmembrane pore. Science, 274:1859–1866. 1996.
363.
StadtmanER. Ascorbic acid and oxidative inactivation of proteins. Am J Clin Nutr, 54,6 Suppl:1125S–1128S. 1991.
364.
StassenFL, CardinaleGJ, UdenfriendS. Activation of prolyl hydroxylase in L-929 fibroblasts by ascorbic acid. Proc Natl Acad Sci U S A, 70:1090–1093. 1973.
365.
SteinbickerAU, BartnikasTB, LohmeyerLK, LeytonP, MayeurC, KaoSM, PappasAE, PetersonRT, BlochDB, YuPB, FlemingMD, BlochKD. Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood, 118:4224–4230. 2011.
366.
StoltzfusR. Defining iron-deficiency anemia in public health terms: a time for reflection. J Nutr, 131:565S–567S. 2001.
367.
SuD, AsardH. Three mammalian cytochromes b561 are ascorbate-dependent ferrireductases. FEBS J, 273:3722–3734. 2006.
368.
SuMA, TrenorCC, FlemingJC, FlemingMD, AndrewsNC. The G185R mutation disrupts function of the iron transporter Nramp2. Blood, 92:2157–2163. 1998.
TakahashiN, TakahashiY, PutnamFW. Complete amino acid sequence of human hemopexin, the heme-binding protein of serum. Proc Natl Acad Sci U S A, 82:73–77. 1985.
372.
TalukderMJR, TakeuchiT, HaradaE. Receptor-mediated transport of lactoferrin into the cerebrospinal fluid via plasma in young calves. J Vet Med Sci, 65:957–964. 2003.
373.
TannoT, MillerJL. Iron loading and overloading due to ineffective erythropoiesis. Adv Hematol, 2010Article ID 3582832010.
374.
TaurogA. Molecular evolution of thyroid peroxidase. Biochimie, 81:557–562. 1999.
375.
TheilEC, GossDJ. Living with iron (and oxygen): questions and answers about iron homeostasis. Chem Rev, 109:4568–4579. 2009.
376.
TheilEC. Iron homeostasis and nutritional iron deficiency. J Nutr, 141:724S–728S. 2011.
377.
TheilEC. Targeting mRNA to regulate iron and oxygen metabolism. Biochem Pharmacol, 59:87–93. 2000.
TolosanoE, AltrudaF. Hemopexin: structure, function, and regulation. DNA Cell Biol, 21:297–306. 2002.
380.
TortiFM, TortiSV. Regulation of ferritin genes and protein. Blood, 99:3505–3516. 2002.
381.
TothI, BridgesKR. Ascorbic acid enhances ferritin mRNA translation by an IRP/aconitase switch. J Biol Chem, 270:19540–19544. 1995.
382.
TranTN, EubanksSK, SchafferKJ, ZhouCY, LinderMC. Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood, 90:4979–4986. 1997.
383.
TrinderD, MorganE, BakerE. The mechanisms of iron uptake by fetal rat hepatocytes in culture. Hepatology, 6:852–858. 1986.
384.
TrinderD, OlynykJK, SlyWS, MorganEH. Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse. Proc Natl Acad Sci U S A, 99:5622–5626. 2002.
385.
TsayJ, YangZ, RossFP, Cunningham-RundlesS, LinH, ColemanR, Mayer-KuckukP, DotySB, GradyRW, GiardinaPJ, BoskeyAL, VogiatziMG. Bone loss caused by iron overload in a murine model: importance of oxidative stress. Blood, 116:2582–2589. 2010.
386.
TsunooH, SussmanHH. Characterization of transferrin binding and specificity of the placental transferrin receptor. Arch Biochem Biophys, 225:42–54. 1983.
387.
TulpuleK, RobinsonSR, BishopGM, DringenR. Uptake of ferrous iron by cultured rat astrocytes. J Neurosci Res, 88:563–571. 2010.
388.
VanoaicaL, DarshanD, RichmanL, SchümannK, KühnLC. Intestinal ferritin H is required for an accurate control of iron absorption. Cell Metab, 12:273–282. 2010.
389.
VargasJD, HerpersB, McKieAT, GledhillS, McDonnellJ, van den HeuvelM, DaviesKE, PontingCP. Stromal cell-derived receptor 2 and cytochrome b561 are functional ferric reductases. Biochim Biophys Acta, 1651:116–123. 2003.
390.
VelascoG, CalS, QuesadaV, SánchezLM, López-OtínC. Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins. J Biol Chem, 277:37637–37646. 2002.
391.
VelkovT, LawenA. Nonribosomal peptide synthetases as technological platforms for the synthesis of highly modified peptide bioeffectors—cyclosporin synthetase as a complex example. Biotechnol Annu Rev, 9:151–197. 2003.
392.
Verga FalzacappaMV, CasanovasG, HentzeMW, MuckenthalerMU. A bone morphogenetic protein (BMP)-responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells. J Mol Med (Berl), 86:531–540. 2008.
393.
VinchiF, GastaldiS, SilengoL, AltrudaF, TolosanoE. Hemopexin prevents endothelial damage and liver congestion in a mouse model of heme overload. Am J Pathol, 173:289–299. 2008.
394.
ViscaP, ImperiF, LamontIL. Pyoverdine siderophores: from biogenesis to biosignificance. Trends Microbiol, 15:22–30. 2007
395.
VolkeM, GaleDP, MaegdefrauU, SchleyG, KlankeB, BosserhoffAK, MaxwellPH, EckardtKU, WarneckeC. Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors. PLoS One, 4:e7875. 2009.
396.
VolzK. The functional duality of iron regulatory protein 1. Curr Opin Struct Biol, 18:106–111. 2008.
397.
VujicSpasić M, KissJ, HerrmannT, GalyB, MartinacheS, StolteJ, GröneH-J, StremmelW, HentzeMW, MuckenthalerMU. Hfe acts in hepatocytes to prevent hemochromatosis. Cell Metab, 7:173–178. 2008.
398.
Vujic SpasicM, KissJ, HerrmannT, KesslerR, StolteJ, GalyB, RathkolbB, WolfE, StremmelW, HentzeMW, MuckenthalerMU. Physiologic systemic iron metabolism in mice deficient for duodenal Hfe. Blood, 109:4511–4517. 2007.
399.
VulpeCD, KuoYM, MurphyTL, CowleyL, AskwithC, LibinaN, GitschierJ, AndersonGJ. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet, 21:195–199. 1999.
400.
WaheedA, ParkkilaS, SaarnioJ, FlemingRE, ZhouXY, TomatsuS, BrittonRS, BaconBR, SlyWS. Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci U S A, 96:1579–1584. 1999.
401.
WallaceDF, SummervilleL, CramptonEM, FrazerDM, AndersonGJ, SubramaniamVN. Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload. Hepatology, 50:1992–2000. 2009.
402.
WallanderML, LeiboldEA, EisensteinRS. Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim Biophys Acta, 1763:668–689. 2006.
403.
WalterPB, FungEB, KillileaDW, JiangQ, HudesM, MaddenJ, PorterJ, EvansP, VichinskyE, HarmatzP. Oxidative stress and inflammation in iron-overloaded patients with β-thalassaemia or sickle cell disease. Br J Haematol, 135:254–263. 2006.
404.
WangJ, SlungaardA. Role of eosinophil peroxidase in host defense and disease pathology. Arch Biochem Biophys, 445:256–260. 2006.
405.
WangJ, ChenG, FilebeenC, PantopoulosK. Insights on regulation and function of the iron regulatory protein 1 (IRP1)Hemoglobin, 32:109–115. 2008.
406.
WangJ, ChenG, MuckenthalerM, GalyB, HentzeMW, PantopoulosK. Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity. Mol Cell Biol, 24:954–965. 2004.
407.
WangJ, FillebeenC, ChenG, BiederbickA, LillR, PantopoulosK. Iron-dependent degradation of apo-IRP1 by the ubiquitin-proteasome pathway. Mol Cell Biol, 27:2423–2430. 2007.
408.
WangR-H, LiC, XuX, ZhengY, XiaoC, ZerfasP, CoopermanS, EckhausM, RouaultT, MishraL, DengC-X. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab, 2:399–409. 2005.
409.
WangW, DiX, D'AgostinoRBJr., TortiSV, TortiFM. Excess capacity of the iron regulatory protein system. J Biol Chem, 282:24650–24659. 2007.
410.
WatkinsJA, AltazanJD, ElderP, LiC-Y, NunezM-T, CuiX-X, GlassJ. Kinetic characterization of reductant dependent processes of iron mobilization from endocytic vesicles. Biochemistry, 31:5820–5830. 1992.
411.
WeatherallDJ. Pathophysiology of thalassaemia. Baillieres Clin Haematol, 11:127–146. 1998.
412.
WeissG. Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta, 1790:682–693. 2009.
413.
WeissG, GoodnoughLT. Anemia of chronic disease. N Engl J Med, 352:1011–1023. 2005.
414.
WestAPJr., GiannettiAM, HerrAB, BennettMJ, NangianaJS, PierceJR, WeinerLP, SnowPM, BjorkmanPJ. Mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites. J Mol Biol, 313:385–397. 2001.
415.
WiesenerMS, JürgensenJS, RosenbergerC, ScholzeCK, HörstrupJH, WarneckeC, MandriotaS, BechmannI, FreiUA, PughCW, RatcliffePJ, BachmannS, MaxwellPH, EckardtK-U. Widespread hypoxia-inducible expression of HIF-2a in distinct cell populations of different organs. FASEB J, 17:271–273. 2003.
WoodMJ, SkoienR, PowellLW. The global burden of iron overload. Hepatol Int, 3:434–444. 2009.
418.
WyllieJC, KaufmanN. An electron microscopic study of heme uptake by rat duodenum. Lab Invest, 47:471–476. 1982.
419.
YamanakaK, IshikawaH, MegumiY, TokunagaF, KanieM, RouaultTA, MorishimaI, MinatoN, IshimoriK, IwaiK. Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2. Nat Cell Biol, 5:336–340. 2003.
420.
YangL, FanM, DuF, GongQ, BiZG, ZhuZJ, ZhuLL, KeY. Hypoxic preconditioning increases iron transport rate in astrocytes. Biochim Biophys Acta, 1822:500–508. 2012.
421.
YeH, RouaultTA. Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry, 49:4945–4956. 2010.
422.
YoungGA, HillGL. Assessment of protein-calorie malnutrition in surgical patients from plasma proteins and anthropometric measurements. Am J Clin Nutr, 31:429–435. 1978.
423.
YoungSP, RobertsS, BomfordA. Intracellular processing of transferrin and iron by isolated rat hepatocytes. Biochem J, 232:819–823. 1985.
424.
YuY, KovacevicZ, RichardsonDR. Tuning cell cycle regulation with an iron key. Cell Cycle, 6:1982–1994. 2007.
425.
ZanellaI, DerosasM, CorradoM, CoccoE, CavadiniP, BiasiottoG, PoliM, VerardiR, ArosioP. The effects of frataxin silencing in HeLa cells are rescued by the expression of human mitochondrial ferritin. Biochim Biophys Acta, 1782:90–98. 2008.
426.
ZhangA-S, Canonne-HergauxF, GruenheidS, GrosP, PonkaP. Use of Nramp2-transfected Chinese hamster ovary cells and reticulocytes from mk/mk mice to study iron transport mechanisms. Exp Hematol, 36:1227–1235. 2008.
427.
ZhangA-S, YangF, MeyerK, HernandezC, Chapman-ArvedsonT, BjorkmanPJ, EnnsCA. Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plasma membrane. J Biol Chem, 283:17494–17502. 2008.
428.
ZhangAS, EnnsCA. Iron homeostasis: recently identified proteins provide insight into novel control mechanisms. J Biol Chem, 284:711–715. 2009.
429.
ZhangA-S, DaviesPS, CarlsonHL, EnnsCA. Mechanisms of HFE-induced regulation of iron homeostasis: insights from the W81A HFE mutation. Proc Natl Acad Sci U S A, 100:9500–9505. 2003.
430.
ZhangA-S, WestAPJr., WymanAE, BjorkmanPJ, EnnsCA. Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. J Biol Chem, 280:33885–33894. 2005.
431.
ZhangA-S, YangF, WangJ, TsukamotoH, EnnsCA. Hemojuvelin-neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression. J Biol Chem, 284:22580–22589. 2009.
432.
ZhangX, RovinBH. Hepcidin expression by human monocytes in response to adhesion and pro-inflammatory cytokines. Biochim Biophys Acta, 1800:1262–1267. 2010.
433.
ZhaoN, GaoJ, EnnsCA, KnutsonMD. ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. J Biol Chem, 285:32141–32150. 2010.
434.
ZhengL, KennedyMC, BlondinGA, BeinertH, ZalkinH. Binding of cytosolic aconitase to the iron responsive element of porcine mitochondrial aconitase mRNA. Arch Biochem Biophys, 299:356–360. 1992.
435.
ZimmerM, EbertBL, NeilC, BrennerK, PapaioannouI, MelasA, TollidayN, LambJ, PantopoulosK, GolubT, IliopoulosO. Small-molecule inhibitors of HIF-2α translation link its 5′UTR iron-responsive element to oxygen sensing. Mol Cell, 32:838–848. 2008.
