Skip to main content

Dynamic Stability of Apoferritin: A New Model to Explain How Impermeable Reagents Can Reduce/Capture Iron within Ferritin

  • Chapter
Iron Biominerals

Abstract

The toxic effects of the essential metal, iron, are controlled within cells through its being bound by proteins or organic chelators [Halliwell and Gutteridge, 1986]. Within mammals, most intracellular iron not utilized for heme-containing enzymes is bound by the iron-storage protein, ferritin [Harrison et al., 1987; Theil, 1987; Joshi and Zimmerman, 1988]. Up to several thousand atoms of ferric iron can be contained within each ferritin molecule as one or more crystallites of the biomineral, ferrihydrite (5Fe2O3·9H2O) [Towe, 1981; Ford et al., 1984]. Unlike commonplace rust, the “biological iron oxide” within ferritin remains soluble. This very special and important capability is a direct consequence of the quaternary structure of the metalloprotein; in each ferritin molecule, the insoluble ferrihydrite forms a core that is contained inside an outer assembly of 24 polypeptide subunits (Mr≈ 20kDa) [Ford et al., 1984]. The core crystallites within the central cavity are attached to the surrounding protein shell [Stuhrmann et al., 1976; Massover, 1978].

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Andersen, M. E., 1971, Sedimentation equilibrium experiments on the self-association of hemoglobin from the lamprey Petromyzon marinus. A model for oxygen transport in the lamprey, J. Biol. Chem., 246:4800–4806.

    PubMed  CAS  Google Scholar 

  • Bakker, G. R. and Boyer, R. F., 1986, Iron incorporation into apoferritin. The role of apoferritin as a ferroxidase, J. Biol. Chem., 261:13182–13185.

    PubMed  CAS  Google Scholar 

  • Bolann, B. J. and Ulvik, R. J., 1987, Release of iron from ferritin by xanthine oxidase. Role of the superoxide radical, Biochem. J., 243:55–59.

    CAS  Google Scholar 

  • Bonomi, F. and Pagani, S., 1986, Removal of ferritin-bound iron by DL-dihydrolipoate and DL-dihydrolipoamide, Europ. J. Biochem., 155, 295–300.

    CAS  Google Scholar 

  • Bonomi, F., Cerioli, A. and Pagani, S., 1989, Molecular aspects of the removal of ferritin-bound iron by DL-dihydrolipoate, Biochim. Biophys. Acta., 994:180–186.

    CAS  Google Scholar 

  • Briehl, R. W., 1963, The relation between the oxygen equilibrium and aggregation of subunits in lamprey hemoglobin, J. Biol. Chem., 238:2361–2366.

    CAS  Google Scholar 

  • Crichton, R. R., Roman, F., Roland, F., Paques, E., Paques, A. and Vandamme, E., 1980, Ferritin iron deposition and mobilisation, J. Mol. Catal., 7:267–276.

    Article  CAS  Google Scholar 

  • Dognin, J., Girardet, J. L. and Chapron, Y., 1973, Etude polarographique de la mobilisation du fer de la ferritine, Biochim. Biophys. Acta., 297:276–284.

    CAS  Google Scholar 

  • Farrant, J. L., 1954, An electron microscopic study of ferritin, Biochim. Biophys. Acta., 13:569–576.

    Article  PubMed  CAS  Google Scholar 

  • Ford, G. C., Harrison, P. M., Rice, D. W., Smith, J. M. A., Treffry, A., White, J. L. and Yariv, J., 1984, Ferritin: design and formation of an iron-storage molecule, Phil. Trans. Roy. Soc. Lond., 304B:551–565.

    Google Scholar 

  • Halliwell, B. and Gutteridge, J. M. C., 1986, Iron and free radical reactions: two aspects of antioxidant protection, TIBS. 11:372–375.

    CAS  Google Scholar 

  • Harris, D. C., 1978, Iron exchange between ferritin and transferrin in Vitro, Biochem., 17:3071–3078.

    Article  CAS  Google Scholar 

  • Harrison, P. M., Clegg, G. A. and May, K., 1980, Ferritin structure and function, In: “Iron in Biochemistry and Medicine, II”, A. Jacobs and M. Worwood, eds., Academic Press, London, pp. 131–171.

    Google Scholar 

  • Harrison, P. M., Ford, G. C., Rice, D. W., Smith, J. M. A., Treffry, A. and White, J. L., 1987, Structural and functional studies on ferritins, Biochem. Soc. Trans., 15:744–748.

    PubMed  CAS  Google Scholar 

  • Hesterberg, L. K. and Lee, J. C., 1982, Self-association of rabbit muscle phosphofructokinase: effect of ligands, Biochem., 21:216–222.

    Article  CAS  Google Scholar 

  • Inoue, S. and Sato, H., 1967, Cell motility by labile association of molecules. The nature of mitotic spindle fibers and their role in chromosome movement, J. Gen Phvsiol., 50:259–288.

    Article  CAS  Google Scholar 

  • Jacobs, D. L., Watt, G. D., Frankel, R. B. and Papaefthymiou, G. C., 1989, Redox reactions associated with iron release from mammalian ferritin, Biochem., 28:1650–1655.

    Article  CAS  Google Scholar 

  • Jones, M. M. and Johnston, D. O., 1967, Rate of release of iron from ferritin to 1,10-phenanthroline, Nature, 216:509–510.

    Article  PubMed  CAS  Google Scholar 

  • Jones, T., Spencer, R. and Walsh, C., 1978, Mechanism and kinetics of iron release from ferritin by dihydro-flavins and dihydroflavin analogues, Biochem., 17: 4011–4017.

    Article  CAS  Google Scholar 

  • Joshi, J. G. and Zimmerman, A., 1988, Ferritin: an expanded role in metabolic regulation, Toxicol., 48:21–29.

    Article  CAS  Google Scholar 

  • Lee, J. C. K., Lee, S. S., Schlesinger, K. J. and Richter, G. W., 1974, Detection of protein subunits of ferritin in situ in cells by immunofluorescence, Amer. J. Pathol., 75:473–487.

    CAS  Google Scholar 

  • Levi, S., Luzzago, A., Cesareni, G., Cozzi, A., Franceschinelli, F., Albertini, A. and Arosio, P., 1988, Mechanism of ferritin iron uptake: activity of the H-chain and deletion mapping of the ferro-oxidase site. A study of iron uptake and ferro-oxidase activity of human liver, recombinant H-chain ferritins, and of two H-chain deletion mutants, J. Biol. Chem., 263:18086–18092.

    PubMed  CAS  Google Scholar 

  • Linder, M. C., Nagel, G. M., Roboz, M. and Hungerford, Jr., D. M., 1981, The size and shape of heart and muscle ferritins analyzed by sedimentation, gel filtration, and electrophoresis, J. Biol. Chem., 256:9104–9110.

    PubMed  CAS  Google Scholar 

  • Luzzago, A., Arosio, P., Iacobello, C., Ruggeri, G., Capucci, L., Brocchi, E., De Simone, F., Gamba, D., Gabri, E., Levi, S., and Albertini, A., 1986, Immunochemical characterization of human liver and heart ferritins with monoclonal antibodies, Biochim. Biophys. Acta., 872:61–71.

    Article  PubMed  CAS  Google Scholar 

  • Margolis, R. L. and Wilson, L., 1978, Opposite end assembly and disassembly of microtubules at steady state in vitro, Cell, 13:1–8.

    Article  PubMed  CAS  Google Scholar 

  • Massover, W. H., 1978, The ultrastructure of ferritin macro-molecules. III. Mineralized iron in ferritin is attached to the protein shell, J. Mol. Biol., 123: 721–726.

    Article  PubMed  CAS  Google Scholar 

  • Massover, W. H., 1979a, Ultrastructural studies on the dissociation of apoferritin into subunits, In: “Proc. 37th. Ann. Meet. Electron Micr. Soc. America”, G. W. Bailey, ed., Claitor’s Publishing Division, Baton Rouge, pp. 22–23.

    Google Scholar 

  • Massover, W. H., 1979b, The resolution of individual protein subunits in ferritin, In: “Electron Microscopy 1978”, J. M. Sturgess, ed., Microscopical Society of Canada, Toronto, 11:182–183.

    Google Scholar 

  • Massover, W. H., 1980, Ultrastructural evidence for the dissociation of free subunits from ferritin upon dilution, Biochem. Biophys. Res. Comm., 96:1427–1433.

    Article  PubMed  CAS  Google Scholar 

  • Massover, W. H. and Cowley, J. M., 1975, Ultrastructure of ferritin and apoferritin, In: “Proteins of Iron Storage and Transport in Biochemistry and Medicine”, R. R. Crichton, ed., North-Holland Publishing Co., Amsterdam, pp. 237–244.

    Google Scholar 

  • Mazur, A., Baez, S. and Shorr, E., 1955, The mechanism of iron release from ferritin as related to its biological properties, J. Biol. Chem., 213:147–160.

    PubMed  CAS  Google Scholar 

  • Mitchison, T. and Kirschner, M., 1984, Dynamic instability of microtubule growth, Nature, 312:237–242.

    Article  PubMed  CAS  Google Scholar 

  • Niederer, W., 1970, Ferritin: iron incorporation and iron release, Experientia. 26:218–220.

    Article  PubMed  CAS  Google Scholar 

  • Pape, L., Multani, J. S., Stitt, C. and Saltman, P., 1968, In Vitro reconstitution of ferritin, Biochem., 7:606–612.

    Article  CAS  Google Scholar 

  • Stefanini, S., Desideri, A., Vecchini, P., Drakenberg, T. and Chiancone, E., 1989, Identification of the iron entry channels in apoferritin. Chemical modification and spectroscopic studies, Biochem., 28:378–382.

    Article  CAS  Google Scholar 

  • Stuhrmann, H. B., Haas, J., Ibel, K., Koch, M. H. J. and Crichton, R. R., 1976, Low angle neutron scattering of ferritin studied by contrast variation, J. Mol. Biol., 100:399–413.

    Article  PubMed  CAS  Google Scholar 

  • Theil, E. C., 1987, Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms, Ann. Rev. Biochem., 56:289–315.

    Article  PubMed  CAS  Google Scholar 

  • Towe, K. M., 1981, Structural distinction between ferritin and iron-dextran (Imferon). An electron diffraction comparison, J. Biol. Chem., 256:9377–9378.

    PubMed  CAS  Google Scholar 

  • Watt, G. D., Jacobs, D. and Frankel, R. B., 1988, Redox reactivity of bacterial and mammalian ferritin: Is reductant entry into the ferritin interior a necessary step for iron release? Proc. Nat. Acad. Sci. USA., 85:7457–7461.

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto, S. and Storey, K. B., 1988, Dissociation-association of lactate dehydrogenase isozymes: influences on the formation of tetramers versus dimers of M4-LDH and H4-LDH, Int. J. Biochem., 20:1261–1265.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Massover, W.H. (1991). Dynamic Stability of Apoferritin: A New Model to Explain How Impermeable Reagents Can Reduce/Capture Iron within Ferritin. In: Frankel, R.B., Blakemore, R.P. (eds) Iron Biominerals. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3810-3_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-3810-3_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6699-7

  • Online ISBN: 978-1-4615-3810-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics