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Ultrastructural aspects of iron storage, transport and metabolism

  • Basic Neurosciences, Genetics and Immunology - Review Article
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Abstract

The iron storage proteins, ferritin and hemosiderin, enable electron microscopic visualization thanks to their electron-dense iron content, which is not present in other compounds involved in transport or metabolism of iron such as transferrin, lactoferrin, or hemoglobin. It is this electron density which contributed to the unraveling of stages in absorption, transport, deposition, storage, and release of iron. In recent years, additional methods of investigation have further supported the information achieved by the ultrastructural studies. Even while using new analytical methods, the seminal morphological observations remain valid for understanding the role of iron in health and disease. In this review, we will illustrate a few basic findings of electron microscopy in humans, experimental animals, and cell cultures. The importance of H chain ferritin as a transporter across the blood–brain barrier is just an example of a new role revealed for an “old” storage protein, explaining some controversial observations on the presence of iron in the brain.

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References

  • Arstila AU, Bradford WD, Kinney TD, Trump BF (1970) Iron metabolism and cell membranes. Am J Path 53:419–449

    Google Scholar 

  • Ben-Shachar D, Finberg JP, Youdim MBH (1985) Effect of iron chelators on dopamine D2 receptors. J Neurochem 45:995–1005

    Google Scholar 

  • Bessis M (1973) Living blood cells and their ultrastructure. Springer, Berlin

    Google Scholar 

  • Clegg GA, Fitton JE, Harrison PM, Trefry A (1980) Ferritin: molecular structure and iron-storage mechanisms. Prog Biophys Mol Biol 36:56–86

    PubMed  CAS  Google Scholar 

  • Cooper PJ, Iancu TC, Ward RJ, Guttridge KM, Peter TJ (1988) Quantitative analysis of immunogold labeling for ferritin in liver from control and iron-overloaded rats. Histochem J 20:499–509

    Article  PubMed  CAS  Google Scholar 

  • Crichton R (2009) Iron metabolism—from molecular mechanisms to clinical consequences, 3rd edn. Wiley, New York

  • Fishbach FA, Gregory DW, Harrison PM, Hoy TG, Williams JM (1971) On the structure of hemosiderin and its relationship to ferritin. J Ultrastruct Res 37:495–503

    Article  Google Scholar 

  • Fisher J, Devraj K, Ingram J, Slagle-Webb B, Madhankumar AB, Liu X, Klinger M (2007) Ferritin: a novel mechanism for delivery of iron to the brain and other organs. Am J Physiol Cell Physiol 293:C641–C649

    Article  PubMed  CAS  Google Scholar 

  • Graham JM, Paley MNJ, Grünewald RA1, Hoggard N, Griffiths PD (2000) Brain iron deposition in Parkinson’s disease imaged using the PRIME magnetic resonance sequence. Brain 123:2423–2431

  • Gregory A, Polster BJ, Hayflick SJ (2009) Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet 46:73–80

    Google Scholar 

  • Harrison PM, Arosio P (1996) The ferritins: molecular proprieties, iron storage function and cellular regulation. Biochim Biophys Acta 1275:161–203

    Article  PubMed  Google Scholar 

  • Harrison PM, Hoy TG, Macara IJ, Hoare RJ (1974) Ferritin iron uptake and release. Structure-function relationships. Biochem J 143:445–451

    PubMed  CAS  Google Scholar 

  • Harrison PM, Clegg GA, May K (1980) Ferritin structure and function. In: Jacobs A, Worwood M (eds) Iron in biochemistry and medicine. Academic Press, London, pp 131–171

  • Hernández-Yago J, Knecht A, Martinez-Ramon, Grisolia S (1980) Autophagy of ferritin incorporated into the cytosol of Hela cells by liposomes. Cell Tissue Res 205:303–309

    Article  PubMed  Google Scholar 

  • Hill JM (1985) Iron concentration reduced in ventral pallidum, globus pallidus, substantia nigra by GABA-transaminase inhibitor, gamma-vinyl GABA. Brain Res 342:18–25

    Article  PubMed  CAS  Google Scholar 

  • Hill JM (1988) The distribution of iron in the brain. In: Youdim MBH (ed) Brain iron: neurochemical and behavioral aspects. Taylor and Francis, London, pp 1–24

  • Hirsh M, Konijn AM, Iancu TC (2002) Acquisition, storage and release of iron by human cultured hepatoma cells. J Hepatol 36:30–38

    Article  PubMed  CAS  Google Scholar 

  • Iancu TC (1983) Iron overload. Mol Aspect Med 6:1–100

    Article  CAS  Google Scholar 

  • Iancu TC (1989a) Iron and neoplasia: ferritin and hemosiderin in tumor cells. Ultrastruct Pathol 13:573–584

    Article  PubMed  CAS  Google Scholar 

  • Iancu TC (1989b) Ultrastructural pathology of iron overload 2:475–495

    CAS  Google Scholar 

  • Iancu TC (1992) Ferritin and hemosiderin in pathological tissues. Electron Microsc Rev 5:209–229

    Article  PubMed  CAS  Google Scholar 

  • Iancu TC, Landing BH, Neustein HB (1977) Pathogenetic mechanisms in hepatic cirrhosis of thalassemia major: light and electron microscopic studies. Pathol Annu 12:171–200

    PubMed  Google Scholar 

  • Iancu TC, Shiloh H, Link G, Bauminger ER, Pinson A, Hershko C (1987a) Ultrastructural pathology of iron-loaded rat myocardial cells in culture. Br J Exp Pathol 68:53–65

    PubMed  CAS  Google Scholar 

  • Iancu TC, Ward RJ, Peters TJ (1987b) Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis. Virchows Arch B Cell Pathol Incl Mol Pathol 53:208–217

    Article  PubMed  CAS  Google Scholar 

  • Iancu TC, Shiloh H, Raja KB, Simpson RJ, Peters TJ, Perl DP, Hsu A, Good PF (1995) The hypotransferrinaemic mouse: ultrastructural and laser microprobe analysis observations. J Pathol 177:83–94

    Article  PubMed  CAS  Google Scholar 

  • Iancu TC, Perl DP, Sternlieb I, Lerner A, Leshinsky E, Kolodny EH, Hsu Amy, Good PF (1996) The application of laser microprobe mass analysis in the study of biological materials. BioMetals 9:57–65

    Article  PubMed  CAS  Google Scholar 

  • Iancu TC, Deugnier Y, Halliday JW, Powell LW, Brissot P (1997) Ultrastructural sequences during iron overload in genetic hemochromatosis. J Hepatol 27:628–638

    Article  PubMed  CAS  Google Scholar 

  • Jellinger K, Kienzel E, Rumpelmair G, Riederer P, Stachelberger H, Ben-Shachar D, Youdim MBH (2006) Iron melanin complex in substantia nigra of Parkinsonian brain: an X-ray analysis. J Neurochem 59:1168–1171

    Article  Google Scholar 

  • Mandel S, Amit Tamar, Bar-Am Orit, Youdim MBH (2007) Iron dysregulation in Alzheimer’s disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein processing regulatory activities as therapeutic agents. Prog Neurobiol 82:348–360

  • Moos T, Rosengren Nielsen T, Skjorringe T, Morgan EH (2007) Iron trafficking inside the brain. J Neurochem 103:1730–1740

    Article  PubMed  CAS  Google Scholar 

  • Perl DP, Good PF (1992) Comparative techniques for determining cellular iron distribution in brain tissues. Ann Neurol 32:S76–S81

    Article  PubMed  CAS  Google Scholar 

  • Richter GW (1958) Electron microscopy of hemosiderin: presence of ferritin and occurrence of crystalline lattices in hemosiderin deposits. J Biophys Biochem Cytol 4:55–58

    Google Scholar 

  • Richter GW (1978) The iron-loaded cell—the cytopathology of iron storage. Am J Pathol 91:362–404

    PubMed  CAS  Google Scholar 

  • Richter GW, Bessis MC (1965) Commentary on hemosiderin. Blood 25:370–374

    PubMed  CAS  Google Scholar 

  • Rouault TA (2001) Iron and the brain. Nat Genet 28:299–300

    Article  PubMed  CAS  Google Scholar 

  • Rouault TA, Zhang DL, Jeong SY (2009) Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins. Met Brain Dis 24:673–684

    Article  CAS  Google Scholar 

  • Takanashi M, Mochizuku H, Yokomizo K, Hattori N, Mori H, Yamamura Y, Mizuno Y (2001) Iron accumulation in the substantia nigra autosomal recessive juvenile parkinsonism (ARJP). Parkinsonism Relat Disord 7:311–314

    Article  PubMed  Google Scholar 

  • Vidnes A, Helgeland L (1973) Sex and age differences in the hemosiderin content of rat liver BBA 328:365–372

    CAS  Google Scholar 

  • Youdim MBH, Yehuda S, Ben-Shachar D, Ashkenazi R (1982) Behavioral and brain biochemical changes in iron-deficient rats: the involvement of iron in dopamine receptor function. In: Pollit E, Leibel RL (eds) Iron deficiency: brain biochemistry and behavior. Raven Press, New York, pp 39–56

  • Zuyderhoudt FMJ, Linthorst C, Hengeveld P (1978) On the iron content of human serum ferritin, especially in acute viral hepatitis and iron overload. Clin Chim Acta 90:93–99

    Google Scholar 

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Acknowledgments

This work was supported by grant 11-2009 by the Dan David Foundation and by a contribution from the Milman Fund for Pediatric Research.

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Authors and Affiliations

  1. Pediatric Research and Electron Microscopy Unit, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 34396, Haifa, Israel

    Theodore C. Iancu

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  1. Theodore C. Iancu
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Correspondence to Theodore C. Iancu.

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Iancu, T.C. Ultrastructural aspects of iron storage, transport and metabolism. J Neural Transm 118, 329–335 (2011). https://doi.org/10.1007/s00702-011-0588-7

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  • DOI: https://doi.org/10.1007/s00702-011-0588-7

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