The role of iron regulatory proteins in mammalian iron homeostasis and disease
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Hentze, M.W., Muckenthaler, M.U. & Andrews, N.C. Balancing acts: molecular control of mammalian iron metabolism. Cell 117, 285–297 (2004).
Aisen, P. Transferrin, the transferrin receptor, and the uptake of iron by cells. Met. Ions Biol. Syst. 35, 585–631 (1998).
Harrison, P.M. & Arosio, P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim. Biophys. Acta 1275, 161–203 (1996).
Rouault, T. & Klausner, R. Regulation of iron metabolism in eukaryotes. Curr. Top. Cell. Regul. 35, 1–19 (1997).
Pantopoulos, K. Iron metabolism and the IRE/IRP regulatory system: an update. Ann. NY Acad. Sci. 1012, 1–13 (2004).
Klausner, R.D., Rouault, T.A. & Harford, J.B. Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 72, 19–28 (1993).
Gruer, M.J., Artymiuk, P.J. & Guest, J.R. The aconitase family: three structural variations on a common theme. Trends Biochem. Sci. 22, 3–6 (1997).
Beinert, H., Kennedy, M.C. & Stout, D.C. Aconitase as iron-sulfur protein, enzyme, and iron-regulatory protein. Chem. Rev. 96, 2335–2373 (1996).
Addess, K.J., Basilion, J.P., Klausner, R.D., Rouault, T.A. & Pardi, A.J. Structure and dynamics of the iron responsive element RNA: implications for binding of the RNA by iron regulatory proteins. J. Mol. Biol. 274, 72–83 (1997).
Gdaniec, Z., Sierzputowska-Gracz, H. & Theil, E.C. Iron regulatory element and internal loop/bulge structure for ferritin mRNA studied by cobalt(III) hexammine binding, molecular modeling, and NMR spectroscopy. Biochemistry 37, 1505–1512 (1998).
Dix, D.J., Lin, P.N., McKenzie, A.R., Walden, W.E. & Theil, E.C. The influence of the base-paired flanking region on structure and function of the ferritin mRNA iron regulatory element. J. Mol. Biol. 231, 230–240 (1993).
Allerson, C.R., Cazzola, M. & Rouault, T.A. Clinical severity and thermodynamic effects of iron-responsive element mutations in hereditary hyperferritinemia-cataract syndrome. J. Biol. Chem. 274, 26439–26447 (1999).
Henderson, B.R., Menotti, E. & Kuhn, L.C. Iron regulatory proteins 1 and 2 bind distinct sets of RNA target sequences. J. Biol. Chem. 271, 4900–4908 (1996).
Butt, J. et al. Differences in the RNA binding sites of iron regulatory proteins and potential target diversity. Proc. Natl. Acad. Sci. USA 93, 4345–4349 (1996).
Meehan, H.A. & Connell, G.J. The hairpin loop but not the bulged C of the iron responsive element is essential for high affinity binding to iron regulatory protein-1. J. Biol. Chem. 276, 14791–14796 (2001).
Menotti, E., Henderson, B.R. & Kuhn, L.C. Translational regulation of mRNAs with distinct IRE sequences by iron regulatory proteins 1 and 2. J. Biol. Chem. 273, 1821–1824 (1998).
Ke, Y., Wu, J., Leibold, E.A., Walden, W.E. & Theil, E.C. 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).
Theil, E.C. & Eisenstein, R.S. Combinatorial mRNA regulation: iron regulatory proteins and iso-iron-responsive elements (iso-IREs). J. Biol. Chem. 275, 40659–40662 (2000).
Ismail, A.R., Lachlan, K.L., Mumford, A.D., Temple, I.K. & Hodgkins, P.R. Hereditary hyperferritinemia cataract syndrome: ocular, genetic, and biochemical findings. Eur. J. Ophthalmol. 16, 153–160 (2006).
Hentze, M.W. et al. Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science 238, 1570–1573 (1987).
Leibold, E.A. & Munro, H.N. Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5′ untranslated region of ferritin heavy- and light-subunit mRNAs. Proc. Natl. Acad. Sci. USA 85, 2171–2175 (1988).
Melefors, O. et al. Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells. J. Biol. Chem. 268, 5974–5978 (1993).
Cooperman, S.S. et al. Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood 106, 1084–1091 (2005).
Kim, H.Y., LaVaute, T., Iwai, K., Klausner, R.D. & Rouault, T.A. Identification of a conserved and functional iron-responsive element in the 5′UTR of mammalian mitochondrial aconitase. J. Biol. Chem. 271, 24226–24230 (1996).
Gray, N.K., Pantopoulos, K., Dandekar, T., Ackrell, B.A. & Hentze, M.W. Translational regulation of mammalian and Drosophila citric-acid cycle enzymes via iron-responsive elements. Proc. Natl. Acad. Sci. USA 93, 4925–4930 (1996).
Schalinske, K.L., Chen, O.S. & Eisenstein, R.S. 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).
Kohler, S.A., Henderson, B.R. & Kuhn, L.C. 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).
Abboud, S. & Haile, D.J. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275, 19906–19912 (2000).
Gunshin, H. et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482–488 (1997).
Kohler, S.A., Menotti, E. & Kuhn, L.C. 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).
Gunshin, H. et al. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett. 509, 309–316 (2001).
Recalcati, S., Tacchini, L., Alberghini, A., Conte, D. & Cairo, G. Oxidative stress-mediated down-regulation of rat hydroxyacid oxidase 1, a liver-specific peroxisomal enzyme. Hepatology 38, 1159–1166 (2003).
Beaumont, C. et al. Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nat. Genet. 11, 444–446 (1995).
Cazzola, M. & Skoda, R.C. Translational pathophysiology: a novel molecular mechanism of human disease. Blood 95, 3280–3288 (2000).
Rouault, T.A. et al. Cloning of the cDNA encoding an RNA regulatory protein–the human iron-responsive element-binding protein. Proc. Natl. Acad. Sci. USA 87, 7958–7962 (1990).
Patino, M.M. & Walden, W.E. Cloning of a functional cDNA for the rabbit ferritin mRNA repressor protein: demonstration of a tissue specific pattern of expression. J. Biol. Chem. 267, 19011–19016 (1992).
Yu, Y., Radisky, E. & Leibold, E.A. The iron-responsive element binding protein: purification, cloning and regulation in rat liver. J. Biol. Chem. 267, 19005–19010 (1992).
Hirling, H. et al. Expression of active iron regulatory factor from a full-length human cDNA by in vitro transcription/translation. Nucleic Acids Res. 20, 33–39 (1992).
Guo, B., Yu, Y. & Leibold, E.A. Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J. Biol. Chem. 269, 24252–24260 (1994).
Samaniego, F., Chin, J., Iwai, K., Rouault, T.A. & Klausner, R.D. Molecular characterization of a second iron responsive element binding protein, iron regulatory protein 2 (IRP2): structure, function and post-translational regulation. J. Biol. Chem. 269, 30904–30910 (1994).
Kaptain, S. et al. A regulated RNA binding protein also possesses aconitase activity. Proc. Natl. Acad. Sci. USA 88, 10109–10113 (1991).
Kennedy, M.C., Mende-Mueller, L., Blondin, G.A. & Beinert, H. Purification and characterization of cytosolic aconitase from beef liver and its relationship to the iron-responsive element binding protein (IRE-BP). Proc. Natl. Acad. Sci. USA 89, 11730–11734 (1992).
Zheng, L., Andrews, P.C., Hermodson, M.A., Dixon, J.E. & Zalkin, H. Cloning and structural characterization of porcine heart aconitase. J. Biol. Chem. 265, 2814–2821 (1990).
Dupuy, J. et al. Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Structure 14, 129–139 (2006).
Hirling, H., Henderson, B.R. & Kuhn, L.C. Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor from its RNA-binding form to cytoplasmic aconitase. EMBO J. 13, 453–461 (1994).
Philpott, C.C., Klausner, R.D. & Rouault, T.A. The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc. Natl. Acad. Sci. USA 91, 7321–7325 (1994).
DeRusso, P.A. et al. Expression of a constitutive mutant of iron regulatory protein 1 abolishes iron homeostasis in mammalian cells. J. Biol. Chem. 270, 15451–15454 (1995).
Wang, J. & Pantopoulos, K. Conditional derepression of ferritin synthesis in cells expressing a constitutive IRP1 mutant. Mol. Cell. Biol. 22, 4638–4651 (2002).
Rouault, T.A. & Klausner, R.D. Iron-sulfur clusters as biosensors of oxidants and iron. Trends Biochem. Sci. 21, 174–177 (1996).
Cairo, G., Recalcati, S., Pietrangelo, A. & Minotti, G. The iron regulatory proteins: targets and modulators of free radical reactions and oxidative damage. Free Radic. Biol. Med. 32, 1237–1243 (2002).
Bouton, C. & Drapier, J.C. Iron regulatory proteins as NO signal transducers. Sci. STKE 2003, pe17 (2003).
Caltagirone, A., Weiss, G. & Pantopoulos, K. 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).
Haile, D.J. et al. Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high affinity RNA binding. Proc. Natl. Acad. Sci. USA 89, 11735–11739 (1992).
Basilion, J.P., Rouault, T.A., Massinople, C.M., Klausner, R.D. & Burgess, W.H. The iron-responsive element-binding protein: localization of the RNA binding site to the aconitase active-site cleft. Proc. Natl. Acad. Sci. USA 91, 574–578 (1994).
Kaldy, P., Menotti, E., Moret, R. & Kuhn, L.C. Identification of RNA-binding surfaces in iron regulatory protein-1. EMBO J. 18, 6073–6083 (1999).
Gegout, V. et al. Ligand-induced structural alterations in human iron regulatory protein-1 revealed by protein footprinting. J. Biol. Chem. 274, 15052–15058 (1999).
Selezneva, A.I., Cavigiolio, G., Theil, E.C., Walden, W.E. & Volz, K. Crystallization and preliminary X-ray diffraction analysis of iron regulatory protein 1 in complex with ferritin IRE RNA. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 62, 249–252 (2006).
Eisenstein, R.S. Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annu. Rev. Nutr. 20, 627–662 (2000).
Johnson, D.C., Dean, D.R., Smith, A.D. & Johnson, M.K. Structure, function, and formation of biological iron-sulfur clusters. Annu. Rev. Biochem. 74, 247–281 (2005).
Lill, R. & Muhlenhoff, U. Iron-sulfur-protein biogenesis in eukaryotes. Trends Biochem. Sci. 30, 133–141 (2005).
Rouault, T.A. & Tong, W.H. Opinion: iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat. Rev. Mol. Cell Biol. 6, 345–351 (2005).
Tong, W.H. & Rouault, T.A. Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab. 3, 199–210 (2006).
Li, K., Tong, W.H., Hughes, R.M. & Rouault, T.A. Roles of the mammalian cytosolic cysteine desulfurase, ISCS, and scaffold protein, ISCU, in iron-sulfur cluster assembly. J. Biol. Chem. 281, 12344–12351 (2006).
Land, T. & Rouault, T.A. Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization. Mol. Cell 2, 807–815 (1998).
Tong, W.H. & Rouault, T. Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J. 19, 5692–5700 (2000).
Tong, W.H., Jameson, G.N., Huynh, B.H. & Rouault, T.A. Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster. Proc. Natl. Acad. Sci. USA 100, 9762–9767 (2003).
Rodriguez-Manzaneque, M.T., Tamarit, J., Belli, G., Ros, J. & Herrero, E. Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes. Mol. Biol. Cell 13, 1109–1121 (2002).
Molina-Navarro, M.M., Casas, C., Piedrafita, L., Belli, G. & Herrero, E. Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria. FEBS Lett. 580, 2273–2280 (2006).
Wingert, R.A. et al. Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436, 1035–1039 (2005).
Cairo, G., Ronchi, R., Recalcati, S., Campanella, A. & Minotti, G. Nitric oxide and peroxynitrite activate the iron regulatory protein-1 of. Biochemistry 41, 7435–7442 (2002).
Mueller, S., Pantopoulos, K., Hubner, C.A., Stremmel, W. & Hentze, M.W. IRP1 activation by extracellular oxidative stress in the perfused rat liver. J. Biol. Chem. 276, 23192–23196 (2001).
Recalcati, S. et al. Iron regulatory proteins 1 and 2 in human monocytes, macrophages and duodenum: expression and regulation in hereditary hemochromatosis and iron deficiency. Haematologica 91, 303–310 (2006).
Missirlis, F. et al. Compartment-specific protection of iron-sulfur proteins by superoxide dismutase. J. Biol. Chem. 278, 47365–47369 (2003).
Clarke, S.L. et al. Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe-S cluster. EMBO J. 25, 544–553 (2006).
Wallace, M.A. et al. Superoxide inhibits 4Fe-4S cluster enzymes involved in amino acid biosynthesis. Cross-compartment protection by CuZn-superoxide dismutase. J. Biol. Chem. 279, 32055–32062 (2004).
Brown, N.M., Kennedy, M.C., Antholine, W.E., Eisenstein, R.S. & Walden, W.E. Detection of a [3Fe-4S] cluster intermediate of cytosolic aconitase in yeast expressing iron regulatory protein 1. Insights into the mechanism of Fe-S cluster cycling. J. Biol. Chem. 277, 7246–7254 (2002).
Gonzalez, D., Drapier, J.C. & Bouton, C. Endogenous nitration of iron regulatory protein-1 (IRP-1) in nitric oxide-producing murine macrophages: further insight into the mechanism of nitration in vivo and its impact on IRP-1 functions. J. Biol. Chem. 279, 43345–43351 (2004).
Pitula, J.S. et al. Selective inhibition of the citrate-to-isocitrate reaction of cytosolic aconitase by phosphomimetic mutation of serine-711. Proc. Natl. Acad. Sci. USA 101, 10907–10912 (2004).
Fillebeen, C., Caltagirone, A., Martelli, A., Moulis, J.M. & Pantopoulos, K. IRP1 Ser-711 is a phosphorylation site, critical for regulation of RNA-binding and aconitase activities. Biochem. J. 388, 143–150 (2005).
Chen, O.S., Schalinske, K.L. & Eisenstein, R.S. 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).
LaVaute, T. et al. Targeted deletion of iron regulatory protein 2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet. 27, 209–214 (2001).
Galy, B. et al. Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood 106, 2580–2589 (2005).
Meyron-Holtz, E.G. et al. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J. 23, 386–395 (2004).
Meyron-Holtz, E.G., Ghosh, M.C. & Rouault, T.A. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306, 2087–2090 (2004).
Koh, H.J. et al. Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism. J. Biol. Chem. 279, 39968–39974 (2004).
Lawlis, V.B. & Roche, T.E. Effect of micromolar Ca2+ on NADH inhibition of bovine kidney alpha-ketoglutarate dehydrogenase complex and possible role of Ca2+ in signal amplification. Mol. Cell. Biochem. 32, 147–152 (1980).
Palmieri, F. et al. Mitochondrial metabolite transporters. Biochim. Biophys. Acta 1275, 127–132 (1996).
Smith, S.R. et al. Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Ann. NY Acad. Sci. 1012, 65–83 (2004).
Zhang, P. et al. Electron tomography of degenerating neurons in mice with abnormal regulation of iron metabolism. J. Struct. Biol. 150, 144–153 (2005).
Kim, H.Y., Klausner, R.D. & Rouault, T.A. Translational repressor activity is equivalent and is quantitatively predicted by in vitro RNA binding for two iron-responsive element binding proteins, IRP1 and IRP2. J. Biol. Chem. 270, 4983–4986 (1995).
Wu, K.J., Polack, A. & Dalla-Favera, R. Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283, 676–679 (1999).
Iwai, K. et al. Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins. Proc. Natl. Acad. Sci. USA 95, 4924–4928 (1998).
Iwai, K., Klausner, R.D. & Rouault, T.A. Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. EMBO J. 14, 5350–5357 (1995).
Guo, B., Phillips, J.D., Yu, Y. & Leibold, E.A. Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J. Biol. Chem. 270, 21645–21651 (1995).
Wang, J. et al. Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity. Mol. Cell. Biol. 24, 954–965 (2004).
Bourdon, E. et al. 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).
Yamanaka, K. et al. Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2. Nat. Cell Biol. 5, 336–340 (2003).
Jeong, J., Rouault, T.A. & Levine, R.L. Identification of a heme-sensing domain in iron regulatory protein 2. J. Biol. Chem. 279, 45450–45454 (2004).
Ishikawa, H. et al. Involvement of heme regulatory motif in heme-mediated ubiquitination and degradation of IRP2. Mol. Cell 19, 171–181 (2005).
Hanson, E.S., Rawlins, M.L. & Leibold, E.A. Oxygen and iron regulation of iron regulatory protein 2. J. Biol. Chem. 278, 40337–40342 (2003).
Schalinske, K.L. & Eisenstein, R.S. Phosphorylation and activation of both iron regulatory proteins 1 and 2 in HL60 cells. J. Biol. Chem. 271, 7168–7176 (1996).