Skip to main content
Springer Nature Link
Log in

Ferritins: iron/oxygen biominerals in protein nanocages

  • Minireview
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Ferritin protein nanocages that form iron oxy biominerals in the central nanometer cavity are nature’s answer to managing iron and oxygen; gene deletions are lethal in mammals and render bacteria more vulnerable to host release of antipathogen oxidants. The multifunctional, multisubunit proteins couple iron with oxygen (maxi-ferritins) or hydrogen peroxide (mini-ferritins) at catalytic sites that are related to di-iron sites oxidases, ribonucleotide reductase, methane monooxygenase and fatty acid desaturases, and synthesize mineral precursors. Gated pores, distributed symmetrically around the ferritin cages, control removal of iron by reductants and chelators. Gene regulation of ferritin, long known to depend on iron and, in animals, on a noncoding messenger RNA (mRNA) structure linked in a combinatorial array to functionally related mRNA of iron transport, has recently been shown to be linked to an array of proteins for antioxidant responses such as thioredoxin and quinone reductases. Ferritin DNA responds more to oxygen signals, and ferritin mRNA responds more to iron signals. Ferritin genes (DNA and RNA) and protein function at the intersection of iron and oxygen chemistry in biology.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Liu X, Theil EC (2005) Acc Chem Res 38:167–175

    Article  PubMed  CAS  Google Scholar 

  2. Pereira AS, Small W, Krebs C, Tavares P, Edmondson DE, Theil EC, Huynh BH (1998) Biochemistry 37:9871–9876

    Article  PubMed  CAS  Google Scholar 

  3. Trikha J, Waldo GS, Lewandowski FA, Ha Y, Theil EC, Weber PC, Allewell NM (1994) Proteins 18:107–118

    Article  PubMed  CAS  Google Scholar 

  4. Yang X, Chasteen ND (1996) Biophys J 71:1587–1595

    PubMed  CAS  Google Scholar 

  5. Ren B, Tibbelin G, Kajino T, Asami O, Ladenstein R (2003) J Mol Biol 329:467–477

    Article  PubMed  CAS  Google Scholar 

  6. Ceci P, Cellai S, Falvo E, Rivetti C, Rossi GL, Chiancone E (2004) Nucleic Acids Res 32:5935–5944

    Article  PubMed  CAS  Google Scholar 

  7. Stillman TJ, Upadhyay M, Norte VA, Sedelnikova SE, Carradus M, Tzokov S, Bullough PA, Shearman CA, Gasson MJ, Williams CH, Artymiuk PJ, Green J (2005) Mol Microbiol 57:1101–1112

    Article  PubMed  CAS  Google Scholar 

  8. Trikha J, Theil EC, Allewell NM (1995) J Mol Biol 248:949–967

    Article  PubMed  CAS  Google Scholar 

  9. Moenne-Loccoz P, Baldwin J, Ley BA, Loehr TM, Bollinger JM Jr (1998) Biochemistry 37:14659–14663

    Article  PubMed  CAS  Google Scholar 

  10. Takagi H, Shi D, Ha Y, Allewell NM, Theil EC (1998) J Biol Chem 273:18685–18688

    Article  PubMed  CAS  Google Scholar 

  11. Broadwater JA, Achim C, Munck E, Fox BG (1999) Biochemistry 38:12197–12204

    Article  PubMed  CAS  Google Scholar 

  12. Jin W, Takagi H, Pancorbo NM, Theil EC (2001) Biochemistry 40:7525–7532

    Article  PubMed  CAS  Google Scholar 

  13. Levi S, Luzzago A, Cesareni G, Cozzi A, Franceschinelli F, Albertini A, Arosio P (1988) J Biol Chem 263:18086–18092

    PubMed  CAS  Google Scholar 

  14. Bauminger ER, Harrison PM, Hechel D, Hodson NW, Nowik I, Treffry A, Yewdall SJ (1993) Biochem J 296:709–719

    PubMed  CAS  Google Scholar 

  15. Baldwin J, Krebs C, Saleh L, Stelling M, Huynh BH, Bollinger JM Jr, Riggs-Gelasco P (2003) Biochemistry 42:13269–13279

    Article  PubMed  CAS  Google Scholar 

  16. Fox BG, Lyle KS, Rogge CE (2004) Acc Chem Res 37:421–429

    Article  PubMed  CAS  Google Scholar 

  17. Macedo S, Romao CV, Mitchell E, Matias PM, Liu MY, Xavier AV, LeGall J, Teixeira M, Lindley P, Carrondo MA (2003) Nat Struct Biol 10:285–290

    Article  PubMed  CAS  Google Scholar 

  18. Ferreira F, Bucchini D, Martin ME, Levi S, Arosio P, Grandchamp B, Beaumont C (2000) J Biol Chem 275:3021–3024

    Article  PubMed  CAS  Google Scholar 

  19. Brenot A, King KY, Caparon MG (1992) Mol Microbiol 55:221–234

    Article  CAS  Google Scholar 

  20. Chen L, Keramati L, Helmann JD (1995) Proc Natl Acad Sci USA 92:8190–8194

    Article  PubMed  CAS  Google Scholar 

  21. Hartford OM, Dowds BC (1994) Microbiology 140:297–304

    Article  PubMed  CAS  Google Scholar 

  22. Kauko A, Haataja S, Pulliainen AT, Finne J, Papageorgiou AC (2004) J Mol Biol 338:547–558

    Article  PubMed  CAS  Google Scholar 

  23. Rocha ER, Owens JG, Smith CJ (2000) J Bacteriol 182:5059–5069

    Article  PubMed  CAS  Google Scholar 

  24. Burton JW, Harlow C, Theil EC (1998) J Plant Nutr 21:913–927

    CAS  Google Scholar 

  25. Theil EC (2004) Annu Rev Nutr 24:327–343

    Article  PubMed  CAS  Google Scholar 

  26. Carrondo MA (2003) EMBO J 22:1959–1968

    Article  PubMed  CAS  Google Scholar 

  27. Lewin AC, Moore GR, Le Brun NE (2005) Dalton Trans 21:3597–3610

    Article  CAS  Google Scholar 

  28. Chiancone E, Ceci P, Ilari A, Ribacchi F, Stefanini S (2004) Biometals 17:197–202

    Article  PubMed  CAS  Google Scholar 

  29. Zhao G, Arosio P, Chasteen ND (2006) Biochemistry 45:3429–3436

    Article  PubMed  CAS  Google Scholar 

  30. Broyles RH, Belegu V, DeWitt CR, Shah SN, Stewart CA, Pye QN, Floyd RA (2001) Proc Natl Acad Sci USA 98:9145–9150

    Article  PubMed  CAS  Google Scholar 

  31. Thompson KJ, Fried MG, Ye Z, Boyer P, Connor JR (2002) J Cell Sci 115:2165–2177

    PubMed  CAS  Google Scholar 

  32. Surguladze N, Patton S, Cozzi A, Fried MG, Connor JR (2005) Biochem J 388:731–740

    Article  PubMed  CAS  Google Scholar 

  33. Martinez A, Kolter R (1997) J Bacteriol 179:5188–5194

    PubMed  CAS  Google Scholar 

  34. Antelmann H, Engelmann S, Schmid R, Sorokin A, Lapidus A, Hecker M (1997) J Bacteriol 179:7251–7256

    PubMed  CAS  Google Scholar 

  35. Grant RA, Filman DJ, Finkel SE, Kolter R, Hogle JM (1998) Nat Struct Biol 5:294–303

    Article  PubMed  CAS  Google Scholar 

  36. Wolf SG, Frenkiel D, Arad T, Finkel SE, Kolter R, Minsky A (1999) Nature 400:83–85

    Article  PubMed  CAS  Google Scholar 

  37. Travers A, Muskhelishvili G (2005) Curr Opin Genet Dev 15:507–514

    Article  PubMed  CAS  Google Scholar 

  38. Waldo GS, Theil EC (1993) Biochemistry 32:13262–13269

    Article  PubMed  CAS  Google Scholar 

  39. Sun S, Arosio P, Levi S, Chasteen ND (1993) Biochemistry 32:9362–9369

    Article  PubMed  CAS  Google Scholar 

  40. Bou-Abdallah F, Zhao G, Mayne HR, Arosio P, Chasteen ND (2005) J Am Chem Soc 127:3885–3893

    Article  PubMed  CAS  Google Scholar 

  41. Liu X, Theil EC (2004) Proc Natl Acad Sci USA 101:8557–8562

    Article  PubMed  CAS  Google Scholar 

  42. Theil EC (2001) In: Messerschmidt A, Huber R, Poulos T, Wieghardt K (eds) Handbook of metalloproteins. Wiley, Chichester, pp 771–781

  43. Pereira AS, Tavares P, Lloyd SG, Danger D, Edmondson DE, Theil EC, Huynh BH (1997) Biochemistry 36:7917–7927

    Article  PubMed  CAS  Google Scholar 

  44. Hwang J, Krebs C, Huynh BH, Edmondson DE, Theil EC, Penner-Hahn JE (2000) Science 287:122–125

    Article  PubMed  CAS  Google Scholar 

  45. Moenne-Loccoz P, Krebs C, Herlihy K, Edmondson DE, Theil EC, Huynh BH, Loehr TM (1999) Biochemistry 38:5290–5295

    Article  PubMed  CAS  Google Scholar 

  46. Shu L, Nesheim JC, Kauffmann K, Munck E, Lipscomb JD, Que L Jr (1997) Science 275:515–518

    Article  PubMed  CAS  Google Scholar 

  47. Rosenzweig AC, Brandstetter H, Whittington DA, Nordlund P, Lippard SJ, Frederick CA (1997) Proteins 29:141–152

    Article  PubMed  CAS  Google Scholar 

  48. Tong W, Burdi D, Riggs-Gelasco P, Chen S, Edmondson D, Huynh BH, Stubbe J, Han S, Arvai A, Tainer J (1998) Biochemistry 37:5840–5848

    Article  PubMed  CAS  Google Scholar 

  49. Broadwater JA, Ai J, Loehr TM, Sanders-Loehr J, Fox BG (1998) Biochemistry 37:14664–14671

    Article  PubMed  CAS  Google Scholar 

  50. Yoon T, Cowan JA (2003) J Am Chem Soc 125:6078–6084

    Article  PubMed  CAS  Google Scholar 

  51. Park S, Gakh O, O’Neill HA, Mangravita A, Nichol H, Ferreira GC, Isaya G (2003) J Biol Chem 278:31340–31351

    Article  PubMed  CAS  Google Scholar 

  52. Yoon T, Cowan JA (2004) J Biol Chem 279:25943–25946

    Article  PubMed  CAS  Google Scholar 

  53. Bulteau AL, O’Neill HA, Kennedy MC, Ikeda-Saito M, Isaya G, Szweda LI (2004) Science 305:242–245

    Article  PubMed  CAS  Google Scholar 

  54. Fraser J, Vieira de Mello L, Ward D, Rees HH, Williams DR, Fang Y, Brass A, Gracey AY, Cossins AR (2006) Proc Natl Acad Sci USA (in press)

  55. Que L Jr (2004) J Biol Inorg Chem 9:684–690

    PubMed  CAS  Google Scholar 

  56. Treffry A, Zhao Z, Quail MA, Guest JR, Harrison PM (1995) Biochemistry 34:15204–15213

    Article  PubMed  CAS  Google Scholar 

  57. Levi S, Luzzago A, Franceschinelli F, Santambrogio P, Cesareni G, Arosio P (1989) Biochem J 264:381–388

    PubMed  CAS  Google Scholar 

  58. Bauminger ER, Harrison PM, Hechel D, Nowik I, Treffry A (1991) Biochim Biophys Acta 118:48–58

    Google Scholar 

  59. Yablonski MJ, Theil EC (1992) Biochemistry 31:9680–9684

    Article  PubMed  CAS  Google Scholar 

  60. Zhao G, Bou-Abdallah F, Yang X, Arosio P, Chasteen ND (2001) Biochemistry 40:10832–10838

    Article  PubMed  CAS  Google Scholar 

  61. Jameson GN, Jin W, Krebs C, Perreira AS, Tavares P, Liu X, Theil EC, Huynh BH (2002) Biochemistry 41:13435–13443

    Article  PubMed  CAS  Google Scholar 

  62. Bou-Abdallah F, Papaefthymiou GC, Scheswohl DM, Stanga SD, Arosio P, Chasteen ND (2002) Biochem J 364:57–63

    PubMed  CAS  Google Scholar 

  63. Fetter J, Cohen J, Danger D, Sanders-Loehr J, Theil EC (1997) J Biol Inorg Chem 2:652–661

    Article  CAS  Google Scholar 

  64. Zhao G, Su M, Chasteen ND (2005) J Mol Biol 352:467–477

    Article  PubMed  CAS  Google Scholar 

  65. Curie C, Briat JF (2003) Annu Rev Plant Biol 2003:183–206

    Article  CAS  Google Scholar 

  66. Chasteen ND, Harrison PM (1999) J Struct Biol 126:182–194

    Article  PubMed  CAS  Google Scholar 

  67. Crichton RR, Roman F, Roland F, Pagues E, Paques A, Vandamme E (1980) J Mol Catal 7:267–276

    Article  CAS  Google Scholar 

  68. Vichinsky EP (2001) Semin Hematol 38:2–4

    Article  PubMed  CAS  Google Scholar 

  69. Vergani P, Basso C, Mense M, Nairn AC, Gadsby DC (2005) Biochem Soc Trans 33:1003–1007

    Article  PubMed  CAS  Google Scholar 

  70. Hempstead PD, Yewdall SJ, Fernie AR, Lawson DM, Artymiuk PJ, Rice DW, Ford GC, Harrison PM (1997) J Mol Biol 268:424–448

    Article  PubMed  CAS  Google Scholar 

  71. Liu X, Jin W, Theil EC (2003) Proc Natl Acad Sci USA 100:3653–3658

    Article  PubMed  CAS  Google Scholar 

  72. Listowsky I, Blauer G, Enlard S, Betheil JJ (1972) Biochemistry 11:2176–2182

    Article  PubMed  CAS  Google Scholar 

  73. Eisenstein RS (2000) Annu Rev Nutr 20:627–662

    Article  PubMed  CAS  Google Scholar 

  74. Hentze MW, Muckenthaler MU, Andrews NC (2004) Cell 117:285–297

    Article  PubMed  CAS  Google Scholar 

  75. Tsuji Y, Ayaki H, Whitman SP, Morrow CS, Torti SV, Torti FM (2000) Mol Cell Biol 16:5818–5827

    Article  Google Scholar 

  76. Torti FM, Torti SV (2002) Blood 99:3505–3516

    Article  PubMed  CAS  Google Scholar 

  77. Hintze KJ, Theil EC (2005) Proc Natl Acad Sci USA 102:15048–15052

    Article  PubMed  CAS  Google Scholar 

  78. Sun J, Brand M, Zenke Y, Tashiro S, Groudine M, Igarashi K (2004) Proc Natl Acad Sci USA 101:1461–1466

    Article  PubMed  CAS  Google Scholar 

  79. Hintze KJ, Wald KA, Zeng H, Jeffery EH, Finley JW (2003) J Nutr 133:2721–2727

    PubMed  CAS  Google Scholar 

  80. Ogawa K, Sun J, Taketani S, Nakajima O, Nishitani C, Sassa S, Hayashi N, Yamamoto M, Shibahara S, Fujita H, Igarashi K (2001) EMBO J 20:2835–2843

    Article  PubMed  CAS  Google Scholar 

  81. Iwasaki K, Mackenzie EL, Hailemariam K, Sakamoto K, Tsuji Y (2006) Mol Cell Biol 26:2845–2856

    Article  PubMed  CAS  Google Scholar 

  82. Miller LL, Miller SC, Torti SV, Tsuji Y, Torti FM (1991) Proc Natl Acad Sci USA 88:4946–4950

    Article  PubMed  CAS  Google Scholar 

  83. Addess KJ, Basilion JP, Klausner RD, Rouault TA, Pardi A (1997) J Mol Biol 274:72–83

    Article  PubMed  CAS  Google Scholar 

  84. Gdaniec Z, Sierzputowska-Gracz H, Theil EC (1998) Biochemistry 37:1505–1512

    Article  PubMed  CAS  Google Scholar 

  85. Wang YH, Sczekan SR, Theil EC (1990) Nucleic Acids Res 18:4463–4468

    Article  PubMed  CAS  Google Scholar 

  86. Tibodeau JD, Fox PM, Ropp PA, Theil EC, Thorp HH (2006) Proc Natl Acad Sci USA 103:253–257

    Article  PubMed  CAS  Google Scholar 

  87. Selezneva AI, Cavigiolio G, Theil EC, Walden WE, Volz K (2006) Acta Crystallogr Sect F 62:249–252

    Article  CAS  Google Scholar 

  88. DeLano WL (2002) The PyMOL molecular graphics system. DeLano Scientific, San Carlos

Download references

Acknowledgments

The intellectual and experimental contributions of former students and postdoctoral fellows in the Theil group and colleagues around the world are gratefully acknowledged. Specialized thanks are due Theil group members Weili Jin and Hidenori Takagi for their work on ferritin pores and Korry Hintze for his work on heme-induced ferritin transcription. The work was supported in part by NIH grants DK20251 and HL56169 (X.L., M.M., E.C.T.), as well as by a fellowship from the Cooley’s Anemia Foundation (X.L.).

Author information

Authors and Affiliations

  1. CHORI (Children’s Hospital Research Institute Oakland), 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA

    Elizabeth C. Theil, Manolis Matzapetakis & Xiaofeng Liu

  2. Department of Nutritional Science and Toxicology, University of California at Berkeley, Berkeley, CA, 94702, USA

    Elizabeth C. Theil

Authors
  1. Elizabeth C. Theil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manolis Matzapetakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaofeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth C. Theil.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Theil, E.C., Matzapetakis, M. & Liu, X. Ferritins: iron/oxygen biominerals in protein nanocages. J Biol Inorg Chem 11, 803–810 (2006). https://doi.org/10.1007/s00775-006-0125-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-006-0125-6

Keywords

Search

Navigation