SpringerLink
Log in

Dynamics of Iron Homeostasis in Health and Disease: Molecular Mechanisms and Methods for Iron Determination

  • Chapter
  • First Online:
Thermodynamics and Biophysics of Biomedical Nanosystems

Part of the book series: Series in BioEngineering ((SERBIOENG))

Abstract

Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite its crucial role in vital biological processes, exceeded iron levels can be harmful for cellular and organismal homeostasis, due to iron’s involvement in the generation of toxic hydroxyl radicals. As such, maintaining balanced iron levels is highly required in order for the organisms to avoid iron toxicity and at the same time preserve iron-dependent processes. This is achieved by the tight coordination of intricate systemic, cellular and subcellular mechanisms for iron absorption, excretion, utilization and storage. Those mechanisms decline during ageing, as well as in multiple human pathologies, leading to iron overload or deprivation, and eventually to death. To gain insight into how perturbations in iron homeostasis lead to disease, it is of great importance to use efficient methods for iron detection in distinct biological samples. Towards this direction, several biochemical and biophysical methods have been developed for the determination of iron and iron-containing compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Puig, S., Ramos-Alonso, L., Romero, A.M., Martinez-Pastor, M.T.: The elemental role of iron in DNA synthesis and repair. Metallomics Integr. Biometal Sci. 9(11), 1483–1500 (2017). https://doi.org/10.1039/c7mt00116a

    Article  Google Scholar 

  2. Veatch, J.R., McMurray, M.A., Nelson, Z.W., Gottschling, D.E.: Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect. Cell 137(7), 1247–1258 (2009). https://doi.org/10.1016/j.cell.2009.04.014

    Article  Google Scholar 

  3. Oexle, H., Gnaiger, E., Weiss, G.: Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation. Biochem. Biophys. Acta. 1413(3), 99–107 (1999)

    Google Scholar 

  4. Coates, T.D.: Physiology and pathophysiology of iron in hemoglobin-associated diseases. Free Radical Biol. Med. 72, 23–40 (2014). https://doi.org/10.1016/j.freeradbiomed.2014.03.039

    Article  Google Scholar 

  5. Winterbourn, C.C.: Toxicity of iron and hydrogen peroxide: the Fenton reaction. Toxicol. Lett. 82–83, 969–974 (1995)

    Article  Google Scholar 

  6. Pantopoulos, K., Porwal, S.K., Tartakoff, A., Devireddy, L.: Mechanisms of mammalian iron homeostasis. Biochemistry 51(29), 5705–5724 (2012). https://doi.org/10.1021/bi300752r

    Article  Google Scholar 

  7. Lawen, A., Lane, D.J.: Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid. Redox Signal. 18(18), 2473–2507 (2013). https://doi.org/10.1089/ars.2011.4271

    Article  Google Scholar 

  8. Harigae, H.: Iron metabolism and related diseases: an overview. Int. J. Hematol. 107(1), 5–6 (2018). https://doi.org/10.1007/s12185-017-2384-0

    Article  Google Scholar 

  9. Anderson, G.J., Frazer, D.M.: Current understanding of iron homeostasis. Am. J. Clin. Nutr. 106(Suppl 6), 1559S–1566S (2017). https://doi.org/10.3945/ajcn.117.155804

    Article  Google Scholar 

  10. Cerami, C.: Iron Nutriture of the Fetus, Neonate, Infant, and Child. Annals of Nutrition and Metabolism 71(suppl 3), 8–14 (2017)

    Article  Google Scholar 

  11. Alwan, N.A., Hamamy, H.: Maternal iron status in pregnancy and long-term health outcomes in the offspring. J. Pediatr. Genet. 4(2), 111–123 (2015). https://doi.org/10.1055/s-0035-1556742

    Article  Google Scholar 

  12. Harrison-Findik, D.D.: Gender-related variations in iron metabolism and liver diseases. World J. Hepatol. 2(8), 302–310 (2010). https://doi.org/10.4254/wjh.v2.i8.302

    Article  Google Scholar 

  13. Joosten, E.: Iron deficiency anemia in older adults: a review. Geriatr. Gerontol. Int. 18(3), 373–379 (2017). https://doi.org/10.1111/ggi.13194

    Article  Google Scholar 

  14. Cao, C., Fleming, M.D.: The placenta: the forgotten essential organ of iron transport. Nutr. Rev. 74(7), 421–431 (2016). https://doi.org/10.1093/nutrit/nuw009

    Article  Google Scholar 

  15. Fuqua, B.K., Vulpe, C.D., Anderson, G.J.: Intestinal iron absorption. J. Trace Elem. Med Biol. 26(2–3), 115–119 (2012). https://doi.org/10.1016/j.jtemb.2012.03.015

    Article  Google Scholar 

  16. Kikuchi, G., Yoshida, T., Noguchi, M.: Heme oxygenase and heme degradation. Biochem. Biophys. Res. Commun. 338(1), 558–567 (2005). https://doi.org/10.1016/j.bbrc.2005.08.020

    Article  Google Scholar 

  17. Le Blanc, S., Garrick, M.D., Arredondo, M.: Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism. Am. J. Physiol. Cell Physiol. 302(12), C1780–C1785 (2012). https://doi.org/10.1152/ajpcell.00080.2012

    Article  Google Scholar 

  18. White, C., Yuan, X., Schmidt, P.J., Bresciani, E., Samuel, T.K., Campagna, D., Hall, C., Bishop, K., Calicchio, M.L., Lapierre, A., Ward, D.M., Liu, P., Fleming, M.D., Hamza, I.: HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metab. 17(2), 261–270 (2013). https://doi.org/10.1016/j.cmet.2013.01.005

    Article  Google Scholar 

  19. Rajagopal, A., Rao, A.U., Amigo, J., Tian, M., Upadhyay, S.K., Hall, C., Uhm, S., Mathew, M.K., Fleming, M.D., Paw, B.H., Krause, M., Hamza, I.: Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins. Nature 453(7198), 1127–1131 (2008). https://doi.org/10.1038/nature06934

    Article  Google Scholar 

  20. Sinclair, J., Pinter, K., Samuel, T., Beardsley, S., Yuan, X., Zhang, J., Meng, K., Yun, S., Krause, M., Hamza, I.: Inter-organ signalling by HRG-7 promotes systemic haem homeostasis. Nat. Cell Biol. 19(7), 799–807 (2017). https://doi.org/10.1038/ncb3539

    Article  Google Scholar 

  21. Lopez, M.A., Martos, F.C.: Iron availability: an updated review. Int. J. Food Sci. Nutr. 55(8), 597–606 (2004). https://doi.org/10.1080/09637480500085820

    Article  Google Scholar 

  22. McKie, A.T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T.J., Farzaneh, F., Hediger, M.A., Hentze, M.W., Simpson, R.J.: A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol. Cell 5(2), 299–309 (2000)

    Article  Google Scholar 

  23. Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S.J., Moynihan, J., Paw, B.H., Drejer, A., Barut, B., Zapata, A., Law, T.C., Brugnara, C., Lux, S.E., Pinkus, G.S., Pinkus, J.L., Kingsley, P.D., Palis, J., Fleming, M.D., Andrews, N.C., Zon, L.I.: Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403(6771), 776–781 (2000). https://doi.org/10.1038/35001596

    Article  Google Scholar 

  24. Nemeth, E., Tuttle, M.S., Powelson, J., Vaughn, M.B., Donovan, A., Ward, D.M., Ganz, T., Kaplan, J.: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306(5704), 2090–2093 (2004). https://doi.org/10.1126/science.1104742

    Article  Google Scholar 

  25. Sangkhae, V., Nemeth, E.: Regulation of the iron homeostatic hormone hepcidin. Adv. Nutr. 8(1), 126–136 (2017). https://doi.org/10.3945/an.116.013961

    Article  Google Scholar 

  26. Casu, C., Nemeth, E., Rivella, S.: Hepcidin agonists as therapeutic tools. Blood 131(16), 1790–1794 (2018). https://doi.org/10.1182/blood-2017-11-737411

    Article  Google Scholar 

  27. Colucci, S., Pagani, A., Pettinato, M., Artuso, I., Nai, A., Camaschella, C., Silvestri, L.: The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes. Blood 130(19), 2111–2120 (2017). https://doi.org/10.1182/blood-2017-04-780692

    Article  Google Scholar 

  28. Pasricha, S.R., Lim, P.J., Duarte, T.L., Casu, C., Oosterhuis, D., Mleczko-Sanecka, K., Suciu, M., Da Silva, A.R., Al-Hourani, K., Arezes, J., McHugh, K., Gooding, S., Frost, J.N., Wray, K., Santos, A., Porto, G., Repapi, E., Gray, N., Draper, S.J., Ashley, N., Soilleux, E., Olinga, P., Muckenthaler, M.U., Hughes, J.R., Rivella, S., Milne, T.A., Armitage, A.E., Drakesmith, H.: Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. Nat. Commun. 8(1), 403 (2017). https://doi.org/10.1038/s41467-017-00500-z

    Article  Google Scholar 

  29. Cassat, J.E., Skaar, E.P.: Iron in infection and immunity. Cell Host Microbe 13(5), 509–519 (2013). https://doi.org/10.1016/j.chom.2013.04.010

    Article  Google Scholar 

  30. Ganz, T., Nemeth, E.: Iron homeostasis in host defence and inflammation. Nat. Rev. Immunol. 15(8), 500–510 (2015). https://doi.org/10.1038/nri3863

    Article  Google Scholar 

  31. Michels, K., Nemeth, E., Ganz, T., Mehrad, B.: Hepcidin and host defense against infectious diseases. PLoS Pathog. 11(8), e1004998 (2015). https://doi.org/10.1371/journal.ppat.1004998

    Article  Google Scholar 

  32. Nevitt, T.: War-Fe-re: iron at the core of fungal virulence and host immunity. Biometals 24(3), 547–558 (2011). https://doi.org/10.1007/s10534-011-9431-8

    Article  Google Scholar 

  33. Deschemin, J.C., Noordine, M.L., Remot, A., Willemetz, A., Afif, C., Canonne-Hergaux, F., Langella, P., Karim, Z., Vaulont, S., Thomas, M., Nicolas, G.: The microbiota shifts the iron sensing of intestinal cells. FASEB J. 30(1), 252–261 (2016). https://doi.org/10.1096/fj.15-276840

    Article  Google Scholar 

  34. Hamilton, D.H., Turcot, I., Stintzi, A., Raymond, K.N.: Large cooperativity in the removal of iron from transferrin at physiological temperature and chloride ion concentration. J. Biol. Inorg. Chem. (JBIC) Publ. Soc. Biol. Inorg. Chem. 9(8), 936–944 (2004). https://doi.org/10.1007/s00775-004-0592-6

    Article  Google Scholar 

  35. He, Q.Y., Mason, A.B., Nguyen, V., MacGillivray, R.T., Woodworth, R.C.: The chloride effect is related to anion binding in determining the rate of iron release from the human transferrin N-lobe. Biochem. J. 350(Pt 3), 909–915 (2000)

    Article  Google Scholar 

  36. Gomme, P.T., McCann, K.B., Bertolini, J.: Transferrin: structure, function and potential therapeutic actions. Drug Discov. Today 10(4), 267–273 (2005). https://doi.org/10.1016/S1359-6446(04)03333-1

    Article  Google Scholar 

  37. Kawabata, H., Germain, R.S., Vuong, P.T., Nakamaki, T., Said, J.W., Koeffler, H.P.: Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. J. Biol. Chem. 275(22), 16618–16625 (2000). https://doi.org/10.1074/jbc.M908846199

    Article  Google Scholar 

  38. Kleven, M.D., Jue, S., Enns, C.A.: Transferrin receptors TfR1 and TfR2 bind transferrin through differing mechanisms. Biochemistry 57(9), 1552–1559 (2018). https://doi.org/10.1021/acs.biochem.8b00006

    Article  Google Scholar 

  39. Mayle, K.M., Le, A.M., Kamei, D.T.: The intracellular trafficking pathway of transferrin. Biochem. Biophys. Acta 1820(3), 264–281 (1820). https://doi.org/10.1016/j.bbagen.2011.09.009

    Article  Google Scholar 

  40. Cmejla, R., Ptackova, P., Petrak, J., Savvulidi, F., Cerny, J., Sebesta, O., Vyoral, D.: Human MRCKalpha is regulated by cellular iron levels and interferes with transferrin iron uptake. Biochem. Biophys. Res. Commun. 395(2), 163–167 (2010). https://doi.org/10.1016/j.bbrc.2010.02.148

    Article  Google Scholar 

  41. Fleming, M.D., Romano, M.A., Su, M.A., Garrick, L.M., Garrick, M.D., Andrews, N.C.: 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(3), 1148–1153 (1998)

    Article  Google Scholar 

  42. Andrews, N.C.: The iron transporter DMT1. Int. J. Biochem. Cell Biol. 31(10), 991–994 (1999)

    Article  Google Scholar 

  43. Jenkitkasemwong, S., Wang, C.Y., Mackenzie, B., Knutson, M.D.: Physiologic implications of metal-ion transport by ZIP14 and ZIP8. Biometals Int. J. Role Metal Ions Biol. Biochem. Med. 25(4), 643–655 (2012). https://doi.org/10.1007/s10534-012-9526-x

    Article  Google Scholar 

  44. Liuzzi, J.P., Aydemir, F., Nam, H., Knutson, M.D., Cousins, R.J.: Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc. Natl. Acad. Sci. U.S.A. 103(37), 13612–13617 (2006). https://doi.org/10.1073/pnas.0606424103

    Article  Google Scholar 

  45. Wang, C.Y., Jenkitkasemwong, S., Duarte, S., Sparkman, B.K., Shawki, A., Mackenzie, B., Knutson, M.D.: ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. J. Biol. Chem. 287(41), 34032–34043 (2012). https://doi.org/10.1074/jbc.M112.367284

    Article  Google Scholar 

  46. Tripathi, A.K., Haldar, S., Qian, J., Beserra, A., Suda, S., Singh, A., Hopfer, U., Chen, S.G., Garrick, M.D., Turner, J.R., Knutson, M.D., Singh, N.: Prion protein functions as a ferrireductase partner for ZIP14 and DMT1. Free Radical Biol. Med. 84, 322–330 (2015). https://doi.org/10.1016/j.freeradbiomed.2015.03.037

    Article  Google Scholar 

  47. Zhao, N., Gao, J., Enns, C.A., Knutson, M.D.: ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. J. Biol. Chem. 285(42), 32141–32150 (2010). https://doi.org/10.1074/jbc.M110.143248

    Article  Google Scholar 

  48. Pinilla-Tenas, J.J., Sparkman, B.K., Shawki, A., Illing, A.C., Mitchell, C.J., Zhao, N., Liuzzi, J.P., Cousins, R.J., Knutson, M.D., Mackenzie, B.: 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(4), C862–C871 (2011). https://doi.org/10.1152/ajpcell.00479.2010

    Article  Google Scholar 

  49. Gunshin, H., Mackenzie, B., Berger, U.V., Gunshin, Y., Romero, M.F., Boron, W.F., Nussberger, S., Gollan, J.L., Hediger, M.A.: Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388(6641), 482–488 (1997). https://doi.org/10.1038/41343

    Article  Google Scholar 

  50. Harrison, P.M., Arosio, P.: The ferritins: molecular properties, iron storage function and cellular regulation. Biochem. Biophys. Acta 1275(3), 161–203 (1996)

    Google Scholar 

  51. Mancias, J.D., Wang, X., Gygi, S.P., Harper, J.W., Kimmelman, A.C.: Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509(7498), 105–109 (2014). https://doi.org/10.1038/nature13148

    Article  Google Scholar 

  52. Vashchenko, G., MacGillivray, R.T.: Multi-copper oxidases and human iron metabolism. Nutrients 5(7), 2289–2313 (2013). https://doi.org/10.3390/nu5072289

    Article  Google Scholar 

  53. Philpott, C.C., Ryu, M.S., Frey, A., Patel, S.: Cytosolic iron chaperones: proteins delivering iron cofactors in the cytosol of mammalian cells. J. Biol. Chem. 292(31), 12764–12771 (2017). https://doi.org/10.1074/jbc.R117.791962

    Article  Google Scholar 

  54. Nandal, A., Ruiz, J.C., Subramanian, P., Ghimire-Rijal, S., Sinnamon, R.A., Stemmler, T.L., Bruick, R.K., Philpott, C.C.: Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2. Cell Metab. 14(5), 647–657 (2011). https://doi.org/10.1016/j.cmet.2011.08.015

    Article  Google Scholar 

  55. Frey, A.G., Nandal, A., Park, J.H., Smith, P.M., Yabe, T., Ryu, M.S., Ghosh, M.C., Lee, J., Rouault, T.A., Park, M.H., Philpott, C.C.: Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase. Proc. Natl. Acad. Sci. U.S.A. 111(22), 8031–8036 (2014). https://doi.org/10.1073/pnas.1402732111

    Article  Google Scholar 

  56. Shi, H., Bencze, K.Z., Stemmler, T.L., Philpott, C.C.: A cytosolic iron chaperone that delivers iron to ferritin. Science 320(5880), 1207–1210 (2008). https://doi.org/10.1126/science.1157643

    Article  Google Scholar 

  57. Leidgens, S., Bullough, K.Z., Shi, H., Li, F., Shakoury-Elizeh, M., Yabe, T., Subramanian, P., Hsu, E., Natarajan, N., Nandal, A., Stemmler, T.L., Philpott, C.C.: Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin. J. Biol. Chem. 288(24), 17791–17802 (2013). https://doi.org/10.1074/jbc.M113.460253

    Article  Google Scholar 

  58. Yanatori, I., Yasui, Y., Tabuchi, M., Kishi, F.: Chaperone protein involved in transmembrane transport of iron. Biochem. J. 462(1), 25–37 (2014). https://doi.org/10.1042/BJ20140225

    Article  Google Scholar 

  59. Muckenthaler, M.U., Galy, B., Hentze, M.W.: Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu. Rev. Nutr. 28, 197–213 (2008). https://doi.org/10.1146/annurev.nutr.28.061807.155521

    Article  Google Scholar 

  60. Wilkinson, N., Pantopoulos, K.: The IRP/IRE system in vivo: insights from mouse models. Front. Pharmacol. 5, 176 (2014). https://doi.org/10.3389/fphar.2014.00176

    Article  Google Scholar 

  61. Hentze, M.W., Caughman, S.W., Rouault, T.A., Barriocanal, J.G., Dancis, A., Harford, J.B., Klausner, R.D.: Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science 238(4833), 1570–1573 (1987)

    Article  Google Scholar 

  62. Hentze, M.W., Rouault, T.A., Caughman, S.W., Dancis, A., Harford, J.B., Klausner, R.D.: A cis-acting element is necessary and sufficient for translational regulation of human ferritin expression in response to iron. Proc. Natl. Acad. Sci. U.S.A. 84(19), 6730–6734 (1987)

    Article  Google Scholar 

  63. Hentze, M.W., Kuhn, L.C.: 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(16), 8175–8182 (1996)

    Article  Google Scholar 

  64. Cmejla, R., Petrak, J., Cmejlova, J.: A novel iron responsive element in the 3′UTR of human MRCKalpha. Biochem. Biophys. Res. Commun. 341(1), 158–166 (2006). https://doi.org/10.1016/j.bbrc.2005.12.155

    Article  Google Scholar 

  65. Lee, P.L., Gelbart, T., West, C., Halloran, C., Beutler, E.: The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cells Mol. Dis. 24(2), 199–215 (1998). https://doi.org/10.1006/bcmd.1998.0186

    Article  Google Scholar 

  66. Salahudeen, A.A., Thompson, J.W., Ruiz, J.C., Ma, H.W., Kinch, L.N., Li, Q., Grishin, N.V., Bruick, R.K.: An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science 326(5953), 722–726 (2009). https://doi.org/10.1126/science.1176326

    Article  Google Scholar 

  67. Vashisht, A.A., Zumbrennen, K.B., Huang, X., Powers, D.N., Durazo, A., Sun, D., Bhaskaran, N., Persson, A., Uhlen, M., Sangfelt, O., Spruck, C., Leibold, E.A., Wohlschlegel, J.A.: Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science 326(5953), 718–721 (2009). https://doi.org/10.1126/science.1176333

    Article  Google Scholar 

  68. Wang, W., Di, X., D’Agostino Jr., R.B., Torti, S.V., Torti, F.M.: Excess capacity of the iron regulatory protein system. J. Biol. Chem. 282(34), 24650–24659 (2007). https://doi.org/10.1074/jbc.M703167200

    Article  Google Scholar 

  69. Meyron-Holtz, E.G., Ghosh, M.C., Iwai, K., LaVaute, T., Brazzolotto, X., Berger, U.V., Land, W., Ollivierre-Wilson, H., Grinberg, A., Love, P., Rouault, T.A.: Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. The EMBO journal 23(2), 386–395 (2004). https://doi.org/10.1038/sj.emboj.7600041

    Article  Google Scholar 

  70. Peyssonnaux, C., Nizet, V., Johnson, R.S.: Role of the hypoxia inducible factors HIF in iron metabolism. Cell Cycle 7(1), 28–32 (2008). https://doi.org/10.4161/cc.7.1.5145

    Article  Google Scholar 

  71. Shah, Y.M., **e, L.: Hypoxia-inducible factors link iron homeostasis and erythropoiesis. Gastroenterology 146(3), 630–642 (2014). https://doi.org/10.1053/j.gastro.2013.12.031

    Article  Google Scholar 

  72. Mole, D.R.: Iron homeostasis and its interaction with prolyl hydroxylases. Antioxid. Redox Signal. 12(4), 445–458 (2010). https://doi.org/10.1089/ars.2009.2790

    Article  Google Scholar 

  73. Lando, D., Peet, D.J., Gorman, J.J., Whelan, D.A., Whitelaw, M.L., Bruick, R.K.: FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 16(12), 1466–1471 (2002). https://doi.org/10.1101/gad.991402

    Article  Google Scholar 

  74. Qian, Z.M., Wu, X.M., Fan, M., Yang, L., Du, F., Yung, W.H., Ke, Y.: Divalent metal transporter 1 is a hypoxia-inducible gene. J. Cell. Physiol. 226(6), 1596–1603 (2011). https://doi.org/10.1002/jcp.22485

    Article  Google Scholar 

  75. Yoshinaga, M., Nakatsuka, Y., Vandenbon, A., Ori, D., Uehata, T., Tsujimura, T., Suzuki, Y., Mino, T., Takeuchi, O.: Regnase-1 maintains iron homeostasis via the degradation of transferrin receptor 1 and prolyl-hydroxylase-domain-containing protein 3 mRNAs. Cell Rep. 19(8), 1614–1630 (2017). https://doi.org/10.1016/j.celrep.2017.05.009

    Article  Google Scholar 

  76. Sanchez, M., Galy, B., Muckenthaler, M.U., Hentze, M.W.: Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency. Nat. Struct. Mol. Biol. 14(5), 420–426 (2007). https://doi.org/10.1038/nsmb1222

    Article  Google Scholar 

  77. Ganz, T., Nemeth, E.: Hepcidin and iron homeostasis. Biochem. Biophys. Acta 1823(9), 1434–1443 (2012). https://doi.org/10.1016/j.bbamcr.2012.01.014

    Article  Google Scholar 

  78. Reichert, C.O., da Cunha, J., Levy, D., Maselli, L.M.F., Bydlowski, S.P., Spada, C.: Hepcidin: homeostasis and diseases related to iron metabolism. Acta Haematol. 137(4), 220–236 (2017). https://doi.org/10.1159/000471838

    Article  Google Scholar 

  79. Hamza, I., Dailey, H.A.: One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans. Biochem. Biophys. Acta. 1823(9), 1617–1632 (2012). https://doi.org/10.1016/j.bbamcr.2012.04.009

    Article  Google Scholar 

  80. Huang, M.L., Lane, D.J., Richardson, D.R.: Mitochondrial mayhem: the mitochondrion as a modulator of iron metabolism and its role in disease. Antioxid. Redox Signal. 15(12), 3003–3019 (2011). https://doi.org/10.1089/ars.2011.3921

    Article  Google Scholar 

  81. Bekri, S., Kispal, G., Lange, H., Fitzsimons, E., Tolmie, J., Lill, R., Bishop, D.F.: Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Blood 96(9), 3256–3264 (2000)

    Google Scholar 

  82. Lane, D.J., Merlot, A.M., Huang, M.L., Bae, D.H., Jansson, P.J., Sahni, S., Kalinowski, D.S., Richardson, D.R.: Cellular iron uptake, trafficking and metabolism: key molecules and mechanisms and their roles in disease. Biochem. Biophys. Acta. 1853(5), 1130–1144 (2015). https://doi.org/10.1016/j.bbamcr.2015.01.021

    Article  Google Scholar 

  83. Lange, H., Kispal, G., Lill, R.: Mechanism of iron transport to the site of heme synthesis inside yeast mitochondria. J. Biol. Chem. 274(27), 18989–18996 (1999)

    Article  Google Scholar 

  84. Zhang, A.S., Sheftel, A.D., Ponka, P.: Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria. Blood 105(1), 368–375 (2005). https://doi.org/10.1182/blood-2004-06-2226

    Article  Google Scholar 

  85. Sheftel, A.D., Zhang, A.S., Brown, C., Shirihai, O.S., Ponka, P.: Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 110(1), 125–132 (2007). https://doi.org/10.1182/blood-2007-01-068148

    Article  Google Scholar 

  86. Shaw, G.C., Cope, J.J., Li, L., Corson, K., Hersey, C., Ackermann, G.E., Gwynn, B., Lambert, A.J., Wingert, R.A., Traver, D., Trede, N.S., Barut, B.A., Zhou, Y., Minet, E., Donovan, A., Brownlie, A., Balzan, R., Weiss, M.J., Peters, L.L., Kaplan, J., Zon, L.I., Paw, B.H.: Mitoferrin is essential for erythroid iron assimilation. Nature 440(7080), 96–100 (2006). https://doi.org/10.1038/nature04512

    Article  Google Scholar 

  87. Paradkar, P.N., Zumbrennen, K.B., Paw, B.H., Ward, D.M., Kaplan, J.: Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol. Cell. Biol. 29(4), 1007–1016 (2009). https://doi.org/10.1128/MCB.01685-08

    Article  Google Scholar 

  88. Chen, W., Paradkar, P.N., Li, L., Pierce, E.L., Langer, N.B., Takahashi-Makise, N., Hyde, B.B., Shirihai, O.S., Ward, D.M., Kaplan, J., Paw, B.H.: Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. Proc. Natl. Acad. Sci. U.S.A. 106(38), 16263–16268 (2009). https://doi.org/10.1073/pnas.0904519106

    Article  Google Scholar 

  89. Sripetchwandee, J., Sanit, J., Chattipakorn, N., Chattipakorn, S.C.: Mitochondrial calcium uniporter blocker effectively prevents brain mitochondrial dysfunction caused by iron overload. Life Sci. 92(4–5), 298–304 (2013). https://doi.org/10.1016/j.lfs.2013.01.004

    Article  Google Scholar 

  90. Zhang, X., Lemasters, J.J.: Translocation of iron from lysosomes to mitochondria during ischemia predisposes to injury after reperfusion in rat hepatocytes. Free Radical Biol. Med. 63, 243–253 (2013). https://doi.org/10.1016/j.freeradbiomed.2013.05.004

    Article  Google Scholar 

  91. Braymer, J.J., Lill, R.: Iron-sulfur cluster biogenesis and trafficking in mitochondria. J. Biol. Chem. 292(31), 12754–12763 (2017). https://doi.org/10.1074/jbc.R117.787101

    Article  Google Scholar 

  92. Adam, A.C., Bornhovd, C., Prokisch, H., Neupert, W., Hell, K.: The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria. EMBO J. 25(1), 174–183 (2006). https://doi.org/10.1038/sj.emboj.7600905

    Article  Google Scholar 

  93. Yoon. T., Cowan. J.A.: Iron-sulfur cluster biosynthesis Characterization of frataxin as an iron donor for assembly of [2Fe–2S] clusters in ISU-type proteins. J. Am. Chem. Soc. 125(20), 6078–6084 (2003). https://doi.org/10.1021/ja027967i

    Article  Google Scholar 

  94. Parent, A., Elduque, X., Cornu, D., Belot, L., Le Caer, J.P., Grandas, A., Toledano, M.B., D’Autreaux, B.: Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols. Nat. Commun. 6, 5686 (2015). https://doi.org/10.1038/ncomms6686

    Article  Google Scholar 

  95. Olive, J.A., Cowan, J.A.: Role of the HSPA9/HSC20 chaperone pair in promoting directional human iron-sulfur cluster exchange involving monothiol glutaredoxin 5. J. Inorg. Biochem. 184, 100–107 (2018). https://doi.org/10.1016/j.**orgbio.2018.04.007

    Article  Google Scholar 

  96. Lill, R., Dutkiewicz, R., Freibert, S.A., Heidenreich, T., Mascarenhas, J., Netz, D.J., Paul, V.D., Pierik, A.J., Richter, N., Stumpfig, M., Srinivasan, V., Stehling, O., Muhlenhoff, U.: The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron-sulfur proteins. Eur. J. Cell Biol. 94(7–9), 280–291 (2015). https://doi.org/10.1016/j.ejcb.2015.05.002

    Article  Google Scholar 

  97. Kim, K.D., Chung, W.H., Kim, H.J., Lee, K.C., Roe, J.H.: Monothiol glutaredoxin Grx5 interacts with Fe–S scaffold proteins Isa1 and Isa2 and supports Fe–S assembly and DNA integrity in mitochondria of fission yeast. Biochem. Biophys. Res. Commun. 392(3), 467–472 (2010). https://doi.org/10.1016/j.bbrc.2010.01.051

    Article  Google Scholar 

  98. Brancaccio, D., Gallo, A., Mikolajczyk, M., Zovo, K., Palumaa, P., Novellino, E., Piccioli, M., Ciofi-Baffoni, S., Banci, L.: Formation of [4Fe–4S] clusters in the mitochondrial iron-sulfur cluster assembly machinery. J. Am. Chem. Soc. 136(46), 16240–16250 (2014). https://doi.org/10.1021/ja507822j

    Article  Google Scholar 

  99. Netz, D.J., Mascarenhas, J., Stehling, O., Pierik, A.J., Lill, R.: Maturation of cytosolic and nuclear iron-sulfur proteins. Trends Cell Biol. 24(5), 303–312 (2014). https://doi.org/10.1016/j.tcb.2013.11.005

    Article  Google Scholar 

  100. 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(3), 199–210 (2006). https://doi.org/10.1016/j.cmet.2006.02.003

    Article  Google Scholar 

  101. Bayeva, M., Khechaduri, A., Wu, R., Burke, M.A., Wasserstrom, J.A., Singh, N., Liesa, M., Shirihai, O.S., Langer, N.B., Paw, B.H., Ardehali, H.: ATP-binding cassette B10 regulates early steps of heme synthesis. Circ. Res. 113(3), 279–287 (2013). https://doi.org/10.1161/CIRCRESAHA.113.301552

    Article  Google Scholar 

  102. Seguin, A., Takahashi-Makise, N., Yien, Y.Y., Huston, N.C., Whitman, J.C., Musso, G., Wallace, J.A., Bradley, T., Bergonia, H.A., Kafina, M.D., Matsumoto, M., Igarashi, K., Phillips, J.D., Paw, B.H., Kaplan, J., Ward, D.M.: Reductions in the mitochondrial ABC transporter Abcb10 affect the transcriptional profile of heme biosynthesis genes. J. Biol. Chem. 292(39), 16284–16299 (2017). https://doi.org/10.1074/jbc.M117.797415

    Article  Google Scholar 

  103. Lange, H., Muhlenhoff, U., Denzel, M., Kispal, G., Lill, R.: The heme synthesis defect of mutants impaired in mitochondrial iron-sulfur protein biogenesis is caused by reversible inhibition of ferrochelatase. J. Biol. Chem. 279(28), 29101–29108 (2004). https://doi.org/10.1074/jbc.M403721200

    Article  Google Scholar 

  104. Santambrogio, P., Biasiotto, G., Sanvito, F., Olivieri, S., Arosio, P., Levi, S.: Mitochondrial ferritin expression in adult mouse tissues. J. Histochem. Cytochem.: Official J. Histochem. Soc. 55(11), 1129–1137 (2007). https://doi.org/10.1369/jhc.7A7273.2007

    Article  Google Scholar 

  105. Gao, G., Chang, Y.Z.: Mitochondrial ferritin in the regulation of brain iron homeostasis and neurodegenerative diseases. Front. Pharmacol. 5, 19 (2014). https://doi.org/10.3389/fphar.2014.00019

    Article  Google Scholar 

  106. 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. 29(3), 376–383 (2002)

    Article  Google Scholar 

  107. Guaraldo, M., Santambrogio, P., Rovelli, E., Di Savino, A., Saglio, G., Cittaro, D., Roetto, A., Levi, S.: Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control. Sci. Rep. 6, 33432 (2016). https://doi.org/10.1038/srep33432

    Article  Google Scholar 

  108. Wu, Q., Wu, W.S., Su, L., Zheng, X., Wu, W.Y., Santambrogio, P., Gou, Y.J., Hao, Q., Wang, P.N., Li, Y.R., Zhao, B.L., Nie, G., Levi, S., Chang, Y.Z.: Mitochondrial ferritin is a hypoxia-inducible factor 1alpha-inducible gene that protects from hypoxia-induced cell death in brain. Antioxid. Redox Sign. 30(2), 198–212 (2019).https://doi.org/10.1089/ars.2017.7063

    Article  Google Scholar 

  109. Nie, G., Sheftel, A.D., Kim, S.F., Ponka, P.: Overexpression of mitochondrial ferritin causes cytosolic iron depletion and changes cellular iron homeostasis. Blood 105(5), 2161–2167 (2005). https://doi.org/10.1182/blood-2004-07-2722

    Article  Google Scholar 

  110. Park, S., Gakh, O., O’Neill, H.A., Mangravita, A., Nichol, H., Ferreira, G.C., Isaya, G.: Yeast frataxin sequentially chaperones and stores iron by coupling protein assembly with iron oxidation. J. Biol. Chem. 278(33), 31340–31351 (2003). https://doi.org/10.1074/jbc.M303158200

    Article  Google Scholar 

  111. Sutak, R., Seguin, A., Garcia-Serres, R., Oddou, J.L., Dancis, A., Tachezy, J., Latour, J.M., Camadro, J.M., Lesuisse, E.: Human mitochondrial ferritin improves respiratory function in yeast mutants deficient in iron-sulfur cluster biogenesis, but is not a functional homologue of yeast frataxin. MicrobiologyOpen 1(2), 95–104 (2012). https://doi.org/10.1002/mbo3.18

    Article  Google Scholar 

  112. Hare, D., Ayton, S., Bush, A., Lei, P.: A delicate balance: iron metabolism and diseases of the brain. Front. Aging Neurosci. 5, 34 (2013). https://doi.org/10.3389/fnagi.2013.00034

    Article  Google Scholar 

  113. Gozzelino, R., Arosio, P.: Iron homeostasis in health and disease. Int. J. Mol. Sci. 17(1), 130 (2016). https://doi.org/10.3390/ijms17010130

    Article  Google Scholar 

  114. Apostolakis, S., Kypraiou, A.M.: Iron in neurodegenerative disorders: being in the wrong place at the wrong time? Rev. Neurosci. 28(8), 893–911 (2017). https://doi.org/10.1515/revneuro-2017-0020

    Article  Google Scholar 

  115. Bilgic, B., Pfefferbaum, A., Rohlfing, T., Sullivan, E.V., Adalsteinsson, E.: MRI estimates of brain iron concentration in normal aging using quantitative susceptibility map**. Neuroimage 59(3), 2625–2635 (2012). https://doi.org/10.1016/j.neuroimage.2011.08.077

    Article  Google Scholar 

  116. Cook, C.I., Yu, B.P.: Iron accumulation in aging: modulation by dietary restriction. Mech. Ageing Dev. 102(1), 1–13 (1998)

    Article  Google Scholar 

  117. James, S.A., Roberts, B.R., Hare, D.J., de Jonge, M.D., Birchall, I.E., Jenkins, N.L., Cherny, R.A., Bush, A.I., McColl, G.: Direct in vivo imaging of ferrous iron dyshomeostasis in ageing Caenorhabditis elegans. Chem. Sci. 6(5), 2952–2962 (2015). https://doi.org/10.1039/c5sc00233h

    Article  Google Scholar 

  118. Lang, M., Braun, C.L., Kanost, M.R., Gorman, M.J.: Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 109(33), 13337–13342 (2012). https://doi.org/10.1073/pnas.1208703109

    Article  Google Scholar 

  119. Schiavi, A., Maglioni, S., Palikaras, K., Shaik, A., Strappazzon, F., Brinkmann, V., Torgovnick, A., Castelein, N., De Henau, S., Braeckman, B.P., Cecconi, F., Tavernarakis, N., Ventura, N.: Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Curr Biol 25(14), 1810–1822 (2015). https://doi.org/10.1016/j.cub.2015.05.059

    Article  Google Scholar 

  120. Klang, I.M., Schilling, B., Sorensen, D.J., Sahu, A.K., Kapahi, P., Andersen, J.K., Swoboda, P., Killilea, D.W., Gibson, B.W., Lithgow, G.J.: Iron promotes protein insolubility and aging in C elegans. Aging (Albany NY) 6(11), 975–991 (2014). https://doi.org/10.18632/aging.100689

    Article  Google Scholar 

  121. Pandolfo, M.: Friedreich ataxia. Arch. Neurol. 65(10), 1296–1303 (2008). https://doi.org/10.1001/archneur.65.10.1296

    Article  Google Scholar 

  122. Campuzano, V., Montermini, L., Molto, M.D., Pianese, L., Cossee, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., Zara, F., Canizares, J., Koutnikova, H., Bidichandani, S.I., Gellera, C., Brice, A., Trouillas, P., De Michele, G., Filla, A., De Frutos, R., Palau, F., Patel, P.I., Di Donato, S., Mandel, J.L., Cocozza, S., Koenig, M., Pandolfo, M.: Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271(5254), 1423–1427 (1996)

    Article  Google Scholar 

  123. Lupoli, F., Vannocci, T., Longo, G., Niccolai, N., Pastore, A.: The role of oxidative stress in Friedreich’s ataxia. FEBS Lett. 592(5), 718–727 (2018). https://doi.org/10.1002/1873-3468.12928

    Article  Google Scholar 

  124. Jasoliya, M.J., McMackin, M.Z., Henderson, C.K., Perlman, S.L., Cortopassi, G.A.: Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans. Hum. Mol. Genet. 26(14), 2627–2633 (2017). https://doi.org/10.1093/hmg/ddx141

    Article  Google Scholar 

  125. Whitnall, M., Suryo Rahmanto, Y., Huang, M.L., Saletta, F., Lok, H.C., Gutierrez, L., Lazaro, F.J., Fleming, A.J., St Pierre, T.G., Mikhael, M.R., Ponka, P., Richardson, D.R.: Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia. Proc. Natl. Acad. Sci. U.S.A. 109(50), 20590–20595 (2012). https://doi.org/10.1073/pnas.1215349109

    Article  Google Scholar 

  126. Tai, G., Corben, L.A., Yiu, E.M., Milne, S.C., Delatycki, M.B.: Progress in the treatment of Friedreich ataxia. Neurol. Neurochir. Pol. 52(2), 129–139 (2018). https://doi.org/10.1016/j.pjnns.2018.02.003

    Article  Google Scholar 

  127. Michel, P.P., Hirsch, E.C., Hunot, S.: Understanding dopaminergic cell death pathways in Parkinson disease. Neuron 90(4), 675–691 (2016). https://doi.org/10.1016/j.neuron.2016.03.038

    Article  Google Scholar 

  128. Peng, Y., Wang, C., Xu, H.H., Liu, Y.N., Zhou, F.: Binding of alpha-synuclein with Fe(III) and with Fe(II) and biological implications of the resultant complexes. J. Inorg. Biochem. 104(4), 365–370 (2010). https://doi.org/10.1016/j.**orgbio.2009.11.005

    Article  Google Scholar 

  129. Golts, N., Snyder, H., Frasier, M., Theisler, C., Choi, P., Wolozin, B.: Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J. Biol. Chem. 277(18), 16116–16123 (2002). https://doi.org/10.1074/jbc.M107866200

    Article  Google Scholar 

  130. Patel, D., Xu, C., Nagarajan, S., Liu, Z., Hemphill, W.O., Shi, R., Uversky, V.N., Caldwell, G.A., Caldwell, K.A., Witt, S.N.: Alpha-synuclein inhibits Snx3-retromer-mediated retrograde recycling of iron transporters in S. cerevisiae and C. elegans models of Parkinson’s disease. Hum Mol Genet 27(9), 1514–1532 (2018). https://doi.org/10.1093/hmg/ddy059

    Article  Google Scholar 

  131. Wan, W., **, L., Wang, Z., Wang, L., Fei, G., Ye, F., Pan, X., Wang, C., Zhong, C.: Iron deposition leads to neuronal alpha-synuclein pathology by inducing autophagy dysfunction. Front. Neurol. 8, 1 (2017). https://doi.org/10.3389/fneur.2017.00001

    Article  Google Scholar 

  132. Chew, K.C., Ang, E.T., Tai, Y.K., Tsang, F., Lo, S.Q., Ong, E., Ong, W.Y., Shen, H.M., Lim, K.L., Dawson, V.L., Dawson, T.M., Soong, T.W.: Enhanced autophagy from chronic toxicity of iron and mutant A53T alpha-synuclein: implications for neuronal cell death in Parkinson disease. J. Biol. Chem. 286(38), 33380–33389 (2011). https://doi.org/10.1074/jbc.M111.268409

    Article  Google Scholar 

  133. Masters, C.L., Bateman, R., Blennow, K., Rowe, C.C., Sperling, R.A., Cummings, J.L.: Alzheimer’s disease. Nat. Rev. Dis. Primers 1, 15056 (2015). https://doi.org/10.1038/nrdp.2015.56

    Article  Google Scholar 

  134. Wan, L., Nie, G., Zhang, J., Luo, Y., Zhang, P., Zhang, Z., Zhao, B.: beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. Free Radic. Biol. Med. 50(1), 122–129 (2011). https://doi.org/10.1016/j.freeradbiomed.2010.10.707

    Article  Google Scholar 

  135. Everett, J., Cespedes, E., Shelford, L.R., Exley, C., Collingwood, J.F., Dobson, J., van der Laan, G., Jenkins, C.A., Arenholz, E., Telling, N.D.: Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer’s disease peptide beta-amyloid(1-42). J. R. Soc. Interface 11(95), 20140165 (2014). https://doi.org/10.1098/rsif.2014.0165

    Article  Google Scholar 

  136. Becerril-Ortega, J., Bordji, K., Freret, T., Rush, T., Buisson, A.: Iron overload accelerates neuronal amyloid-beta production and cognitive impairment in transgenic mice model of Alzheimer’s disease. Neurobiol. Aging 35(10), 2288–2301 (2014). https://doi.org/10.1016/j.neurobiolaging.2014.04.019

    Article  Google Scholar 

  137. Rival, T., Page, R.M., Chandraratna, D.S., Sendall, T.J., Ryder, E., Liu, B., Lewis, H., Rosahl, T., Hider, R., Camargo, L.M., Shearman, M.S., Crowther, D.C., Lomas, D.A.: Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer’s disease. Eur. J. Neurosci. 29(7), 1335–1347 (2009). https://doi.org/10.1111/j.1460-9568.2009.06701.x

    Article  Google Scholar 

  138. Guo, C., Wang, T., Zheng, W., Shan, Z.Y., Teng, W.P., Wang, Z.Y.: Intranasal deferoxamine reverses iron-induced memory deficits and inhibits amyloidogenic APP processing in a transgenic mouse model of Alzheimer’s disease. Neurobiol. Aging 34(2), 562–575 (2013). https://doi.org/10.1016/j.neurobiolaging.2012.05.009

    Article  Google Scholar 

  139. Guo, C., Wang, P., Zhong, M.L., Wang, T., Huang, X.S., Li, J.Y., Wang, Z.Y.: Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem. Int. 62(2), 165–172 (2013). https://doi.org/10.1016/j.neuint.2012.12.005

    Article  Google Scholar 

  140. Lei, P., Ayton, S., Finkelstein, D.I., Spoerri, L., Ciccotosto, G.D., Wright, D.K., Wong, B.X., Adlard, P.A., Cherny, R.A., Lam, L.Q., Roberts, B.R., Volitakis, I., Egan, G.F., McLean, C.A., Cappai, R., Duce, J.A., Bush, A.I.: Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat. Med. 18(2), 291–295 (2012). https://doi.org/10.1038/nm.2613

    Article  Google Scholar 

  141. Fleming, M.D.: Congenital sideroblastic anemias: iron and heme lost in mitochondrial translation. Hematol. Am. Soc. Hematol. Educ. Program. 2011, 525–531 (2011). https://doi.org/10.1182/asheducation-2011.1.525

    Article  Google Scholar 

  142. Guernsey, D.L., Jiang, H., Campagna, D.R., Evans, S.C., Ferguson, M., Kellogg, M.D., Lachance, M., Matsuoka, M., Nightingale, M., Rideout, A., Saint-Amant, L., Schmidt, P.J., Orr, A., Bottomley, S.S., Fleming, M.D., Ludman, M., Dyack, S., Fernandez, C.V., Samuels, M.E.: Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat. Genet. 41(6), 651–653 (2009). https://doi.org/10.1038/ng.359

    Article  Google Scholar 

  143. Lichtenstein, D.A., Crispin, A.W., Sendamarai, A.K., Campagna, D.R., Schmitz-Abe, K., Sousa, C.M., Kafina, M.D., Schmidt, P.J., Niemeyer, C.M., Porter, J., May, A., Patnaik, M.M., Heeney, M.M., Kimmelman, A., Bottomley, S.S., Paw, B.H., Markianos, K., Fleming, M.D.: A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia. Blood 128(15), 1913–1917 (2016). https://doi.org/10.1182/blood-2016-05-719062

    Article  Google Scholar 

  144. Torraco, A., Bianchi, M., Verrigni, D., Gelmetti, V., Riley, L., Niceta, M., Martinelli, D., Montanari, A., Guo, Y., Rizza, T., Diodato, D., Di Nottia, M., Lucarelli, B., Sorrentino, F., Piemonte, F., Francisci, S., Tartaglia, M., Valente, E.M., Dionisi-Vici, C., Christodoulou, J., Bertini, E., Carrozzo, R.: A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia. Clin. Genet. 91(3), 441–447 (2017). https://doi.org/10.1111/cge.12790

    Article  Google Scholar 

  145. D’Hooghe, M., Selleslag, D., Mortier, G., Van Coster, R., Vermeersch, P., Billiet, J., Bekri, S.: X-linked sideroblastic anemia and ataxia: a new family with identification of a fourth ABCB7 gene mutation. Eur. J. Paediatr. Neurol. 16(6), 730–735 (2012). https://doi.org/10.1016/j.ejpn.2012.02.003

    Article  Google Scholar 

  146. Shimada, Y., Okuno, S., Kawai, A., Shinomiya, H., Saito, A., Suzuki, M., Omori, Y., Nishino, N., Kanemoto, N., Fujiwara, T., Horie, M., Takahashi, E.: Cloning and chromosomal map** of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia. J. Hum. Genet. 43(2), 115–122 (1998). https://doi.org/10.1007/s100380050051

    Article  Google Scholar 

  147. Pondarre, C., Campagna, D.R., Antiochos, B., Sikorski, L., Mulhern, H., Fleming, M.D.: Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. Blood 109(8), 3567–3569 (2007). https://doi.org/10.1182/blood-2006-04-015768

    Article  Google Scholar 

  148. Pondarre, C., Antiochos, B.B., Campagna, D.R., Clarke, S.L., Greer, E.L., Deck, K.M., McDonald, A., Han, A.P., Medlock, A., Kutok, J.L., Anderson, S.A., Eisenstein, R.S., Fleming, M.D.: The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum. Mol. Genet. 15(6), 953–964 (2006). https://doi.org/10.1093/hmg/ddl012

    Article  Google Scholar 

  149. Gonzalez-Cabo, P., Bolinches-Amoros, A., Cabello, J., Ros, S., Moreno, S., Baylis, H.A., Palau, F., Vazquez-Manrique, R.P.: Disruption of the ATP-binding cassette B7 (ABTM-1/ABCB7) induces oxidative stress and premature cell death in Caenorhabditis elegans. J. Biol. Chem. 286(24), 21304–21314 (2011). https://doi.org/10.1074/jbc.M110.211201

    Article  Google Scholar 

  150. Nikoletopoulou, V., Kyriakakis, E., Tavernarakis, N.: Cellular and molecular longevity pathways: the old and the new. Trends Endocrinol. Metab. 25(4), 212–223 (2014). https://doi.org/10.1016/j.tem.2013.12.003

    Article  Google Scholar 

  151. Wingert, R.A., Galloway, J.L., Barut, B., Foott, H., Fraenkel, P., Axe, J.L., Weber, G.J., Dooley, K., Davidson, A.J., Schmid, B., Paw, B.H., Shaw, G.C., Kingsley, P., Palis, J., Schubert, H., Chen, O., Kaplan, J., Zon, L.I., Tubingen Screen, C.: Deficiency of glutaredoxin 5 reveals Fe–S clusters are required for vertebrate haem synthesis. Nature 436(7053), 1035–1039 (2005). https://doi.org/10.1038/nature03887

    Article  Google Scholar 

  152. Ye, H., Jeong, S.Y., Ghosh, M.C., Kovtunovych, G., Silvestri, L., Ortillo, D., Uchida, N., Tisdale, J., Camaschella, C., Rouault, T.A.: Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J. Clin. Invest. 120(5), 1749–1761 (2010). https://doi.org/10.1172/JCI40372

    Article  Google Scholar 

  153. Burrage, L.C., Tang, S., Wang, J., Donti, T.R., Walkiewicz, M., Luchak, J.M., Chen, L.C., Schmitt, E.S., Niu, Z., Erana, R., Hunter, J.V., Graham, B.H., Wong, L.J., Scaglia, F.: Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G > A) in the mitochondrial encoded ATP6 gene. Mol Genet Metab 113(3), 207–212 (2014). https://doi.org/10.1016/j.ymgme.2014.06.004

    Article  Google Scholar 

  154. Riley, L.G., Rudinger-Thirion, J., Schmitz-Abe, K., Thorburn, D.R., Davis, R.L., Teo, J., Arbuckle, S., Cooper, S.T., Campagna, D.R., Frugier, M., Markianos, K., Sue, C.M., Fleming, M.D., Christodoulou, J.: LARS2 variants associated with hydrops, lactic acidosis, sideroblastic anemia, and multisystem failure. JIMD Rep. 28, 49–57 (2016). https://doi.org/10.1007/8904_2015_515

    Article  Google Scholar 

  155. Chakraborty, P.K., Schmitz-Abe, K., Kennedy, E.K., Mamady, H., Naas, T., Durie, D., Campagna, D.R., Lau, A., Sendamarai, A.K., Wiseman, D.H., May, A., Jolles, S., Connor, P., Powell, C., Heeney, M.M., Giardina, P.J., Klaassen, R.J., Kannengiesser, C., Thuret, I., Thompson, A.A., Marques, L., Hughes, S., Bonney, D.K., Bottomley, S.S., Wynn, R.F., Laxer, R.M., Minniti, C.P., Moppett, J., Bordon, V., Geraghty, M., Joyce, P.B., Markianos, K., Rudner, A.D., Holcik, M., Fleming, M.D.: Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood 124(18), 2867–2871 (2014). https://doi.org/10.1182/blood-2014-08-591370

    Article  Google Scholar 

  156. Schmitz-Abe, K., Ciesielski, S.J., Schmidt, P.J., Campagna, D.R., Rahimov, F., Schilke, B.A., Cuijpers, M., Rieneck, K., Lausen, B., Linenberger, M.L., Sendamarai, A.K., Guo, C., Hofmann, I., Newburger, P.E., Matthews, D., Shimamura, A., Snijders, P.J., Towne, M.C., Niemeyer, C.M., Watson, H.G., Dziegiel, M.H., Heeney, M.M., May, A., Bottomley, S.S., Swinkels, D.W., Markianos, K., Craig, E.A., Fleming, M.D.: Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9. Blood 126(25), 2734–2738 (2015). https://doi.org/10.1182/blood-2015-09-659854

    Article  Google Scholar 

  157. Lim, S.C., Friemel, M., Marum, J.E., Tucker, E.J., Bruno, D.L., Riley, L.G., Christodoulou, J., Kirk, E.P., Boneh, A., DeGennaro, C.M., Springer, M., Mootha, V.K., Rouault, T.A., Leimkuhler, S., Thorburn, D.R., Compton, A.G.: Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes. Hum. Mol. Genet. 22(22), 4460–4473 (2013). https://doi.org/10.1093/hmg/ddt295

    Article  Google Scholar 

  158. Olsson, A., Lind, L., Thornell, L.E., Holmberg, M.: Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Hum. Mol. Genet. 17(11), 1666–1672 (2008). https://doi.org/10.1093/hmg/ddn057

    Article  Google Scholar 

  159. Mochel, F., Knight, M.A., Tong, W.H., Hernandez, D., Ayyad, K., Taivassalo, T., Andersen, P.M., Singleton, A., Rouault, T.A., Fischbeck, K.H., Haller, R.G.: Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am. J. Hum. Genet. 82(3), 652–660 (2008). https://doi.org/10.1016/j.ajhg.2007.12.012

    Article  Google Scholar 

  160. Kollberg, G., Tulinius, M., Melberg, A., Darin, N., Andersen, O., Holmgren, D., Oldfors, A., Holme, E.: Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain 132(Pt 8), 2170–2179 (2009). https://doi.org/10.1093/brain/awp152

    Article  Google Scholar 

  161. Cameron, J.M., Janer, A., Levandovskiy, V., Mackay, N., Rouault, T.A., Tong, W.H., Ogilvie, I., Shoubridge, E.A., Robinson, B.H.: Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. Am. J. Hum. Genet. 89(4), 486–495 (2011). https://doi.org/10.1016/j.ajhg.2011.08.011

    Article  Google Scholar 

  162. Navarro-Sastre, A., Tort, F., Stehling, O., Uzarska, M.A., Arranz, J.A., Del Toro, M., Labayru, M.T., Landa, J., Font, A., Garcia-Villoria, J., Merinero, B., Ugarte, M., Gutierrez-Solana, L.G., Campistol, J., Garcia-Cazorla, A., Vaquerizo, J., Riudor, E., Briones, P., Elpeleg, O., Ribes, A., Lill, R.: A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe–S proteins. Am. J. Hum. Genet. 89(5), 656–667 (2011). https://doi.org/10.1016/j.ajhg.2011.10.005

    Article  Google Scholar 

  163. Calvo, S.E., Tucker, E.J., Compton, A.G., Kirby, D.M., Crawford, G., Burtt, N.P., Rivas, M., Guiducci, C., Bruno, D.L., Goldberger, O.A., Redman, M.C., Wiltshire, E., Wilson, C.J., Altshuler, D., Gabriel, S.B., Daly, M.J., Thorburn, D.R., Mootha, V.K.: High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat. Genet. 42(10), 851–858 (2010). https://doi.org/10.1038/ng.659

    Article  Google Scholar 

  164. Mittler, R., Darash-Yahana, M., Sohn, Y.S., Bai, F., Song, L., Cabantchik, I.Z., Jennings, P.A., Onuchic, J.N., Nechushtai, R.: NEET proteins: a new link between iron metabolism, reactive oxygen species, and cancer. Antioxid Redox Signal. (2018). https://doi.org/10.1089/ars.2018.7502

    Article  Google Scholar 

  165. Amr, S., Heisey, C., Zhang, M., **a, X.J., Shows, K.H., Ajlouni, K., Pandya, A., Satin, L.S., El-Shanti, H., Shiang, R.: A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am. J. Hum. Genet. 81(4), 673–683 (2007). https://doi.org/10.1086/520961

    Article  Google Scholar 

  166. Rouzier, C., Moore, D., Delorme, C., Lacas-Gervais, S., Ait-El-Mkadem, S., Fragaki, K., Burte, F., Serre, V., Bannwarth, S., Chaussenot, A., Catala, M., Yu-Wai-Man, P., Paquis-Flucklinger, V.: A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions. Hum. Mol. Genet. 26(9), 1599–1611 (2017). https://doi.org/10.1093/hmg/ddx060

    Article  Google Scholar 

  167. Simcox, J.A., McClain, D.A.: Iron and diabetes risk. Cell Metab. 17(3), 329–341 (2013). https://doi.org/10.1016/j.cmet.2013.02.007

    Article  Google Scholar 

  168. Gabrielsen, J.S., Gao, Y., Simcox, J.A., Huang, J., Thorup, D., Jones, D., Cooksey, R.C., Gabrielsen, D., Adams, T.D., Hunt, S.C., Hopkins, P.N., Cefalu, W.T., McClain, D.A.: Adipocyte iron regulates adiponectin and insulin sensitivity. J. Clin. Invest. 122(10), 3529–3540 (2012). https://doi.org/10.1172/JCI44421

    Article  Google Scholar 

  169. Gao, Y., Li, Z., Gabrielsen, J.S., Simcox, J.A., Lee, S.H., Jones, D., Cooksey, B., Stoddard, G., Cefalu, W.T., McClain, D.A.: Adipocyte iron regulates leptin and food intake. J. Clin. Invest. 125(9), 3681–3691 (2015). https://doi.org/10.1172/JCI81860

    Article  Google Scholar 

  170. von Haehling, S., Jankowska, E.A., van Veldhuisen, D.J., Ponikowski, P., Anker, S.D.: Iron deficiency and cardiovascular disease. Nat. Rev. Cardiol. 12(11), 659–669 (2015). https://doi.org/10.1038/nrcardio.2015.109

    Article  Google Scholar 

  171. Kraml, P.: The role of iron in the pathogenesis of atherosclerosis. Physiol. Res. 66(Supplementum 1), S55–S67 (2017)

    Google Scholar 

  172. Sullivan, J.L.: Iron and the genetics of cardiovascular disease. Circulation 100(12), 1260–1263 (1999)

    Article  Google Scholar 

  173. Hanahan, D., Weinberg, R.A.: Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011). https://doi.org/10.1016/j.cell.2011.02.013

    Article  Google Scholar 

  174. Torti, S.V., Torti, F.M.: Iron and cancer: more ore to be mined. Nat. Rev. Cancer 13(5), 342–355 (2013). https://doi.org/10.1038/nrc3495

    Article  Google Scholar 

  175. Bogdan, A.R., Miyazawa, M., Hashimoto, K., Tsuji, Y.: Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem. Sci. 41(3), 274–286 (2016). https://doi.org/10.1016/j.tibs.2015.11.012

    Article  Google Scholar 

  176. Pinnix, Z.K., Miller, L.D., Wang, W., D’Agostino Jr., R., Kute, T., Willingham, M.C., Hatcher, H., Tesfay, L., Sui, G., Di, X., Torti, S.V., Torti, F.M.: Ferroportin and iron regulation in breast cancer progression and prognosis. Sci Transl Med 2(43), 43–56 (2010). https://doi.org/10.1126/scisignal.3001127

    Article  Google Scholar 

  177. Lu, B., Chen, X.B., Ying, M.D., He, Q.J., Cao, J., Yang, B.: The role of ferroptosis in cancer development and treatment response. Front. Pharmacol. 8, 992 (2017). https://doi.org/10.3389/fphar.2017.00992

    Article  Google Scholar 

  178. Dixon, S.J., Lemberg, K.M., Lamprecht, M.R., Skouta, R., Zaitsev, E.M., Gleason, C.E., Patel, D.N., Bauer, A.J., Cantley, A.M., Yang, W.S., Morrison 3rd, B., Stockwell, B.R.: Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5), 1060–1072 (2012). https://doi.org/10.1016/j.cell.2012.03.042

    Article  Google Scholar 

  179. Jiang, L., Kon, N., Li, T., Wang, S.J., Su, T., Hibshoosh, H., Baer, R., Gu, W.: Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520(7545), 57–62 (2015). https://doi.org/10.1038/nature14344

    Article  Google Scholar 

  180. Yang, W.S., SriRamaratnam, R., Welsch, M.E., Shimada, K., Skouta, R., Viswanathan, V.S., Cheah, J.H., Clemons, P.A., Shamji, A.F., Clish, C.B., Brown, L.M., Girotti, A.W., Cornish, V.W., Schreiber, S.L., Stockwell, B.R.: Regulation of ferroptotic cancer cell death by GPX4. Cell 156(1–2), 317–331 (2014). https://doi.org/10.1016/j.cell.2013.12.010

    Article  Google Scholar 

  181. Muller, P.A., Vousden, K.H.: Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell 25(3), 304–317 (2014). https://doi.org/10.1016/j.ccr.2014.01.021

    Article  Google Scholar 

  182. Eskelinen, S., Haikonen, M., Raisanen, S.: Ferene-S as the chromogen for serum iron determinations. Scand. J. Clin. Lab. Invest. 43(5), 453–455 (1983)

    Article  Google Scholar 

  183. Stookey, L.L.: Ferrozine—a new spectrophotometric reagent for iron. Anal. Chem. 42(7), 779–781 (1970). https://doi.org/10.1021/ac60289a016

    Article  Google Scholar 

  184. Moss, M.L., Mellon, M.G.: Colorimetric determination of iron with 2,2′-bipyridyl and with 2,2′,2′-terpyridyl. Ind. Eng. Chem. Anal. Ed. 14(11), 862–865 (1942). https://doi.org/10.1021/i560111a014

    Article  Google Scholar 

  185. Goodwin, J.F., Murphy, B.: The colorimetric determination of iron in biological material with reference to its measurement during chelation therapy. Clinical chemistry 12(2), 58–69 (1966)

    Google Scholar 

  186. Holmes-Hampton, G.P., Tong, W.H., Rouault, T.A.: Biochemical and biophysical methods for studying mitochondrial iron metabolism. Methods Enzymol. 547, 275–307 (2014). https://doi.org/10.1016/B978-0-12-801415-8.00015-1

    Article  Google Scholar 

  187. Fish, W.W.: Rapid colorimetric micromethod for the quantitation of complexed iron in biological samples. Methods Enzymol. 158, 357–364 (1988)

    Article  Google Scholar 

  188. Gao, X., Lu, Y., He, S., Li, X., Chen, W.: Colorimetric detection of iron ions (III) based on the highly sensitive plasmonic response of the N-acetyl-l-cysteine-stabilized silver nanoparticles. Anal. Chim. Acta 879, 118–125 (2015). https://doi.org/10.1016/j.aca.2015.04.002

    Article  Google Scholar 

  189. Kim, K., Nam, Y.S., Lee, Y., Lee, K.B.: Highly sensitive colorimetric assay for determining Fe(3+) based on gold nanoparticles conjugated with glycol chitosan. J. Anal. Methods Chem. 2017, 3648564 (2017). https://doi.org/10.1155/2017/3648564

    Article  Google Scholar 

  190. Jackson, K.W.: Electrothermal atomic absorption spectrometry and related techniques. Anal. Chem. 72(12), 159R–167R (2000)

    Article  Google Scholar 

  191. Payá-pérez, A., Sala, J., Mousty, F.: Comparison of ICP-AES and ICP-MS for the analysis of trace elements in soil extracts. Int. J. Environ. Anal. Chem. 51(1–4), 223–230 (1993). https://doi.org/10.1080/03067319308027628

    Article  Google Scholar 

  192. Çlolak, N., Gümgüm, B.: Determination of Iron by ICP-AES in stereoregular poly(propylene oxide) prepared by Pruitt-Baggett catalyst. Polym.-Plast. Technol. Eng. 33(1), 105–109 (1994). https://doi.org/10.1080/03602559408010734

    Article  Google Scholar 

  193. Bok-Badura, J., Jakobik-Kolon, A., Turek, M., Boncel, S., Karon, K.: A versatile method for direct determination of iron content in multi-wall carbon nanotubes by inductively coupled plasma atomic emission spectrometry with slurry sample introduction. RSC Adv. 5(123), 101634–101640 (2015). https://doi.org/10.1039/c5ra22269a

    Article  Google Scholar 

  194. Profrock, D., Prange, A.: Inductively coupled plasma-mass spectrometry (ICP-MS) for quantitative analysis in environmental and life sciences: a review of challenges, solutions, and trends. Appl. Spectrosc. 66(8), 843–868 (2012). https://doi.org/10.1366/12-06681

    Article  Google Scholar 

  195. Fiorito, V., Geninatti Crich, S., Silengo, L., Altruda, F., Aime, S., Tolosano, E.: Assessment of iron absorption in mice by ICP-MS measurements of (57)Fe levels. Eur. J. Nutr. 51(7), 783–789 (2012). https://doi.org/10.1007/s00394-011-0256-6

    Article  Google Scholar 

  196. Wheal, M.S., DeCourcy-Ireland, E., Bogard, J.R., Thilsted, S.H., Stangoulis, J.C.: Measurement of haem and total iron in fish, shrimp and prawn using ICP-MS: Implications for dietary iron intake calculations. Food Chem. 201, 222–229 (2016). https://doi.org/10.1016/j.foodchem.2016.01.080

    Article  Google Scholar 

  197. Segura, M., Madrid, Y., Camara, C.: Elimination of calcium and argon interferences in iron determination by ICP-MS using desferrioxamine chelating agent immobilized in sol-gel and cold plasma conditions. J. Anal. At. Spectrom. 18(9), 1103–1108 (2003). https://doi.org/10.1039/b301719m

    Article  Google Scholar 

  198. Hu, Q.-H.: Simultaneous separation and quantification of iron and transition species using LC-ICP-MS. Am. J. Anal. Chem. 02(6), 675–682 (2011). https://doi.org/10.4236/ajac.2011.26077

    Article  Google Scholar 

  199. Tanner, S.D., Baranov. V.: A dynamic reaction cell for inductively coupled plasma mass spectrometry (ICP-DRC-MS). II. Reduction Interferences Produced Cell 10 (1999). https://doi.org/10.1016/s1044-0305(99)00081-1

    Article  Google Scholar 

  200. Nestor, S.L., Bancroft, J.D., Gamble, M.: Techn. Neuropathol. (2008)

    Google Scholar 

  201. Brunt, E.M., Olynyk, J.K., Britton, R.S., Janney, C.G., Di Bisceglie, A.M., Bacon, B.R.: Histological evaluation of iron in liver biopsies: relationship to HFE mutations. Am. J. Gastroenterol. 95(7), 1788–1793 (2000). https://doi.org/10.1111/j.1572-0241.2000.02175.x

    Article  Google Scholar 

  202. Deugnier Yves, M., Turlin, B., Moirand, R., Loréal, O., Brissot, P., Powell Lawrie, W., Summers Kim, M., Fletcher, L., Halliday June, W.: Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of a histological hepatic iron index: a study of 192 cases. Hepatology 17(1), 30–34 (1993). https://doi.org/10.1002/hep.1840170107

    Article  Google Scholar 

  203. Ortega, L., Ladero, J.M., Carreras, M.P., Alvarez, T., Taxonera, C., Oliván, M.P., Sanz-Esponera, J., Díaz-Rubio, M.: A computer-assisted morphometric quantitative analysis of iron overload in liver biopsies. A comparison with histological and biochemical methods. Pathol. Res. Pract. 201(10), 673–677 (2005). https://doi.org/10.1016/j.prp.2005.07.002

    Article  Google Scholar 

  204. Hall, A.P., Davies, W., Stamp, K., Clamp, I., Bigley, A.: Comparison of computerized image analysis with traditional semiquantitative scoring of Perls’ Prussian blue stained hepatic iron deposition. Toxicol. Pathol. 41(7), 992–1000 (2013). https://doi.org/10.1177/0192623313476576

    Article  Google Scholar 

  205. Hansen, L.D., Litchman, W.M., Daub, G.H.: Turnbull’s blue and Prussian blue: KFe(III)[Fe(II)(CN)6]. J. Chem. Educ. 46(1), 46 (1969). https://doi.org/10.1021/ed046p46

    Article  Google Scholar 

  206. Pavlishchuk Vitaly, V., Koval Iryna, A., Goreshnik, E., Addison Anthony, W., van Albada Gerard, A., Reedijk, J.: The first example of a true “Turnbull’s Blue” family compound with trapped iron oxidation states. Eur. J. Inorg. Chem. 1, 297–301 (2001). https://doi.org/10.1002/1099-0682(20011)2001:1%3c297:aid-ejic297%3e3.0.co;2-n

    Article  Google Scholar 

  207. Reynolds, E.J.: LXIII—the composition of Prussian blue and Turnbull’s blue. J. Chem. Soc. Trans. 51(0), 644–646 (1887). https://doi.org/10.1039/ct8875100644

    Article  Google Scholar 

  208. Meguro, R., Asano, Y., Odagiri, S., Li, C., Iwatsuki, H., Shoumura, K.: Nonheme-iron histochemistry for light and electron microscopy: a historical, theoretical and technical review. Arch. Histol. Cytol. 70(1), 1–19 (2007)

    Article  Google Scholar 

  209. Aronova, M.A., Leapman, R.D.: Elemental map** by electron energy loss spectroscopy in biology. Methods Mol. Biol. 950, 209–226 (2013). https://doi.org/10.1007/978-1-62703-137-0_13

    Article  Google Scholar 

  210. Kapp, N., Studer, D., Gehr, P., Geiser, M.: Electron energy-loss spectroscopy as a tool for elemental analysis in biological specimens. In: Kuo, J. (ed.) Electron Microscopy: Methods and Protocols, pp. 431–447. Humana Press, Totowa, NJ (2007). https://doi.org/10.1007/978-1-59745-294-6_21

    Google Scholar 

  211. Leapman, R.D.: Detecting single atoms of calcium and iron in biological structures by electron energy-loss spectrum-imaging. J. Microsc. 210(Pt 1), 5–15 (2003)

    Article  MathSciNet  Google Scholar 

  212. van Manen, H.-J., Kraan, Y.M., Roos, D., Otto, C.: Intracellular chemical imaging of heme-containing enzymes involved in innate immunity using resonance raman microscopy. J. Phys. Chem. B 108(48), 18762–18771 (2004). https://doi.org/10.1021/jp046955b

    Article  Google Scholar 

  213. Atkins, C.G., Buckley, K., Blades, M.W., Turner, R.F.B.: Raman spectroscopy of blood and blood components. Appl. Spectrosc. 71(5), 767–793 (2017). https://doi.org/10.1177/0003702816686593

    Article  Google Scholar 

  214. Wang, H., Lee, A.M.D., Lui, H., McLean, D.I., Zeng, H.: A method for accurate in vivo micro-Raman spectroscopic measurements under guidance of advanced microscopy imaging. Sci. Rep. 3, 1890 (2013). https://doi.org/10.1038/srep01890

    Article  Google Scholar 

  215. Al-Qenaei, A., Yiakouvaki, A., Reelfs, O., Santambrogio, P., Levi, S., Hall, N.D., Tyrrell, R.M., Pourzand, C.: Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide. Free Radical Biol. Med. 68, 87–100 (2014). https://doi.org/10.1016/j.freeradbiomed.2013.12.006

    Article  Google Scholar 

  216. Carney, I.J., Kolanowski, J.L., Lim, Z., Chekroun, B., Torrisi, A.G., Hambley, T.W., New, E.J.: A ratiometric iron probe enables investigation of iron distribution within tumour spheroids. Metallomics: Integr. Biometal Sci. 10(4), 553–556 (2018). https://doi.org/10.1039/c7mt00297a

    Article  Google Scholar 

  217. Long, L., Wang, N., Han, Y., Huang, M., Yuan, X., Cao, S., Gong, A., Wang, K.: A coumarin-based fluorescent probe for monitoring labile ferrous iron in living systems. Analyst (2018). https://doi.org/10.1039/c8an00556g

    Article  Google Scholar 

  218. Aron, A.T., Heffern, M.C., Lonergan, Z.R., Vander Wal, M.N., Blank, B.R., Spangler, B., Zhang, Y., Park, H.M., Stahl, A., Renslo, A.R., Skaar, E.P., Chang, C.J.: In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection. Proc. Natl. Acad. Sci. U.S.A. 114(48), 12669–12674 (2017). https://doi.org/10.1073/pnas.1708747114

    Article  Google Scholar 

  219. Jiang, N., Cheng, T., Wang, M., Chan, G.C., **, L., Li, H., Sun, H.: Tracking iron-associated proteomes in pathogens by a fluorescence approach. Metallomics: Integr. Biometal Sci. 10(1), 77–82 (2018). https://doi.org/10.1039/c7mt00275k

    Article  Google Scholar 

  220. Ralle, M., Lutsenko, S.: Quantitative imaging of metals in tissues. Biometals: Int. J. Role Metal Ions Biol. Biochem. Med. 22(1), 197–205 (2009). https://doi.org/10.1007/s10534-008-9200-5

    Article  Google Scholar 

  221. Collingwood, J.F., Davidson, M.R.: The role of iron in neurodegenerative disorders: insights and opportunities with synchrotron light. Front. Pharmacol. 5, 191 (2014). https://doi.org/10.3389/fphar.2014.00191

    Article  Google Scholar 

  222. Punshon, T., Ricachenevsky, F.K., Hindt, M., Socha, A.L., Zuber, H.: Methodological approaches for using synchrotron X-ray fluorescence (SXRF) imaging as a tool in ionomics: examples from Arabidopsis thaliana. Metallomics: Integr. Biometal Sci. 5(9), 1133–1145 (2013). https://doi.org/10.1039/c3mt00120b

    Article  Google Scholar 

  223. Kashiv, Y., Austin 2nd, J.R., Lai, B., Rose, V., Vogt, S., El-Muayed, M.: Imaging trace element distributions in single organelles and subcellular features. Sci. Rep. 6, 21437 (2016). https://doi.org/10.1038/srep21437

    Article  Google Scholar 

  224. Ducic, T., Barski, E., Salome, M., Koch, J.C., Bahr, M., Lingor, P.: X-ray fluorescence analysis of iron and manganese distribution in primary dopaminergic neurons. J. Neurochem. 124(2), 250–261 (2013). https://doi.org/10.1111/jnc.12073

    Article  Google Scholar 

  225. Henry, Y.A.: Basic EPR Methodology. In: Nitric Oxide Research from Chemistry to Biology, pp. 47–60. Springer, Boston, MA, US (1997). https://doi.org/10.1007/978-1-4613-1185-0_4

    Chapter  Google Scholar 

  226. Taiwo, F.A.: Electron paramagnetic resonance spectroscopic studies of iron and copper proteins. Spectroscopy 17(1) (2003). https://doi.org/10.1155/2003/673567

    Article  Google Scholar 

  227. Telser, J., van Slageren, J., Vongtragool, S., Dressel, M., Reiff, W.M., Zvyagin, S.A., Ozarowski, A., Krzystek, J.: High-frequency/high-field EPR spectroscopy of the high-spin ferrous ion in hexaaqua complexes. Magn. Reson. Chem.: MRC 43(Spec no), S130–S139 (2005). https://doi.org/10.1002/mrc.1689

    Article  Google Scholar 

  228. Zhang, Y., Gan, Q.-F., Pavel, E.G., Sigal, E., Solomon, E.I.: EPR definition of the non-heme ferric active sites of mammalian 15-lipoxygenases: major spectral differences relative to human 5-lipoxygenases and plant lipoxygenases and their ligand field origin. J. Am. Chem. Soc. 117(28), 7422–7427 (1995). https://doi.org/10.1021/ja00133a015

    Article  Google Scholar 

  229. Brautigan, D.L., Feinberg, B.A., Hoffman, B.M., Margoliash, E., Preisach, J., Blumberg, W.E.: Multiple low spin forms of the cytochrome c ferrihemochrome. EPR spectra of various eukaryotic and prokaryotic cytochromes c. J. Biol. Chem. 252(2), 574–582 (1977)

    Google Scholar 

  230. Bertrand, P., Janot, J.M., Benosman, H., Gayda, J.P., Labeyrie, F.: An EPR study of the interactions between heme and flavin in yeast flavocytochrome b2. Eur. Biophys. J. 14(5), 273–278 (1987). https://doi.org/10.1007/bf00254891

    Article  Google Scholar 

  231. Walker, F.A.: NMR and EPR spectroscopy of paramagnetic metalloporphyrins and heme proteins. In: Handbook of Porphyrin Science, pp. 1–337. World Scientific Publishing Company (2012). https://doi.org/10.1142/9789814307246_0001

    Google Scholar 

  232. Iwasaki, T., Samoilova, R.I., Kounosu, A., Ohmori, D., Dikanov, S.A.: Continuous-wave and pulsed EPR characterization of the [2Fe–2S](Cys)3(His)1 cluster in rat MitoNEET. J. Am. Chem. Soc. 131(38), 13659–13667 (2009). https://doi.org/10.1021/ja903228w

    Article  Google Scholar 

  233. Priem, A.H., Klaassen, A.A.K., Reijerse, E.J., Meyer, T.E., Luchinat, C., Capozzi, F., Dunham, W.R., Hagen, W.R.: EPR analysis of multiple forms of [4Fe–4S]3+ clusters in HiPIPs. J. Biol. Inorg. Chem. 10(4), 417–424 (2005). https://doi.org/10.1007/s00775-005-0656-2

    Article  Google Scholar 

  234. Bhave, D.P., Hong, J.A., Lee, M., Jiang, W., Krebs, C., Carroll, K.S.: Spectroscopic studies on the [4Fe–4S] cluster in adenosine 5′-phosphosulfate reductase from Mycobacterium tuberculosis. J. Biol. Chem. 286(2), 1216–1226 (2011). https://doi.org/10.1074/jbc.M110.193722

    Article  Google Scholar 

  235. Bonomi, F., Iametti, S., Morleo, A., Ta, D., Vickery, L.E.: Facilitated transfer of IscU–[2Fe2S] clusters by chaperone-mediated ligand exchange. Biochemistry 50(44), 9641–9650 (2011). https://doi.org/10.1021/bi201123z

    Article  Google Scholar 

  236. Chandramouli, K., Johnson, M.K.: HscA and HscB stimulate [2Fe–2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction. Biochemistry 45(37), 11087–11095 (2006). https://doi.org/10.1021/bi061237w

    Article  Google Scholar 

  237. Shakamuri, P., Zhang, B., Johnson, M.K.: Monothiol glutaredoxins function in storing and transporting [Fe2S2] clusters assembled on IscU scaffold proteins. J. Am. Chem. Soc. 134(37), 15213–15216 (2012). https://doi.org/10.1021/ja306061x

    Article  Google Scholar 

  238. Baker, T.M., Nakashige, T.G., Nolan, E.M., Neidig, M.L.: Magnetic circular dichroism studies of iron(ii) binding to human calprotectin. Chem. Sci. 8(2), 1369–1377 (2017). https://doi.org/10.1039/c6sc03487j

    Article  Google Scholar 

  239. Holmes-Hampton, G.P., Jhurry, N.D., McCormick, S.P., Lindahl, P.A.: Iron content of Saccharomyces cerevisiae cells grown under iron-deficient and iron-overload conditions. Biochemistry 52(1), 105–114 (2013). https://doi.org/10.1021/bi3015339

    Article  Google Scholar 

  240. Garber Morales, J., Holmes-Hampton, G.P., Miao, R., Guo, Y., Munck, E., Lindahl, P.A.: Biophysical characterization of iron in mitochondria isolated from respiring and fermenting yeast. Biochemistry 49(26), 5436–5444 (2010). https://doi.org/10.1021/bi100558z

    Article  Google Scholar 

  241. Nienhaus, K., Nienhaus, G.U.: Probing heme protein-ligand interactions by UV/visible absorption spectroscopy. Methods Mol. Biol. 305, 215–242 (2005). https://doi.org/10.1385/1-59259-912-5:215

    Article  Google Scholar 

  242. Berry, E.A., Trumpower, B.L.: Simultaneous determination of hemes a, b, and c from pyridine hemochrome spectra. Anal. Biochem. 161(1), 1–15 (1987)

    Article  Google Scholar 

  243. Mapolelo, D.T., Zhang, B., Naik, S.G., Huynh, B.H., Johnson, M.K.: Spectroscopic and functional characterization of iron-sulfur cluster-bound forms of Azotobacter vinelandii (Nif)IscA. Biochemistry 51(41), 8071–8084 (2012). https://doi.org/10.1021/bi3006658

    Article  Google Scholar 

  244. Albrecht, A.G., Netz, D.J., Miethke, M., Pierik, A.J., Burghaus, O., Peuckert, F., Lill, R., Marahiel, M.A.: SufU is an essential iron-sulfur cluster scaffold protein in Bacillus subtilis. J. Bacteriol. 192(6), 1643–1651 (2010). https://doi.org/10.1128/JB.01536-09

    Article  Google Scholar 

Download references

Acknowledgements

CP is financially supported by General Secretariat for Research and Technology (GSRT), the Hellenic Foundation for Research and Innovation (HFRI) [Scholarship code: 1324], by grants from the European Research Council (ERC – GA695190 – MANNA, ERC – GA737599 – NeuronAgeScreen) and from the BIOIMAGING-GR-MIS5002755, which is co-financed by Greece and the European Union (European Regional Development Fund). E.K. is supported by the Stiftung für Herz- und Kreislaufkrankheiten.

Author information

Authors and Affiliations

  1. Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Crete, Greece

    Christina Ploumi & Nektarios Tavernarakis

  2. Biozentrum, University of Basel, Basel, Switzerland

    Emmanouil Kyriakakis

Authors
  1. Christina Ploumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emmanouil Kyriakakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nektarios Tavernarakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nektarios Tavernarakis .

Editor information

Editors and Affiliations

  1. School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece

    Costas Demetzos

  2. School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece

    Natassa Pippa

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ploumi, C., Kyriakakis, E., Tavernarakis, N. (2019). Dynamics of Iron Homeostasis in Health and Disease: Molecular Mechanisms and Methods for Iron Determination. In: Demetzos, C., Pippa, N. (eds) Thermodynamics and Biophysics of Biomedical Nanosystems. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-13-0989-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-0989-2_5

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-0988-5

  • Online ISBN: 978-981-13-0989-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation