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Copper redistribution in Atox1-deficient mouse fibroblast cells

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Abstract

Quantitative synchrotron X-ray fluorescence (SXRF) imaging of adherent mouse fibroblast cells deficient in antioxidant-1 (Atox1), a metallochaperone protein responsible for delivering Cu to cuproenzymes in the trans-Golgi network, revealed striking differences in the subcellular Cu distribution compared with wild-type cells. Whereas the latter showed a pronounced perinuclear localization of Cu, the Atox1-deficient cells displayed a mostly unstructured and diffuse distribution throughout the entire cell body. Comparison of the SXRF elemental maps for Zn and Fe of the same samples showed no marked differences between the two cell lines. The data underscore the importance of Atox1, not only as a metallochaperone for delivering Cu to cuproenzymes, but also as a key player in maintaining the proper distribution and organization of Cu at the cellular level.

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Abbreviations

Atox1:

Antioxidant-1

BCS:

Bathocuproine disulfonate

PBS:

Phosphate-buffered saline

SXRF:

Synchrotron X-ray fluorescence

TGN:

trans-Golgi network

XRF:

X-ray fluorescence

References

  1. Massaro EJ (ed) (2002) Handbook of copper pharmacology and toxicology. Humana Press, Totowa

  2. Stohs SJ, Bagchi D (1995) Free Radic Biol Med 18:321–336

    Article  PubMed  CAS  Google Scholar 

  3. Valko M, Morris H, Cronin MTD (2005) Curr Med Chem 12:1161–1208

    Article  PubMed  CAS  Google Scholar 

  4. Harris ED (2000) Ann Rev Nutr 20:291–310

    Article  CAS  Google Scholar 

  5. Puig S, Thiele DJ (2002) Curr Opin Chem Biol 6:171–180

    Article  PubMed  CAS  Google Scholar 

  6. Kim B-E, Nevitt T, Thiele DJ (2008) Nat Chem Biol 4:176–185

    Article  PubMed  CAS  Google Scholar 

  7. Bertinato J, L’Abbé MR (2004) J Nutr Biochem 15:316–322

    Article  PubMed  CAS  Google Scholar 

  8. Lalioti V, Muruais G, Tsuchiya Y, Pulido D, Sandoval IV (2009) Front Biosci 14:4878–4903

    PubMed  Google Scholar 

  9. Turski ML, Thiele DJ (2009) J Biol Chem 284:717–721

    Article  PubMed  CAS  Google Scholar 

  10. Andrews NC (2002) Curr Opin Chem Biol 6:181–186

    Article  PubMed  CAS  Google Scholar 

  11. de Bie P, Muller P, Wijmenga C, Klomp LWJ (2007) J Med Genet 44:673–688

    Article  PubMed  CAS  Google Scholar 

  12. Loudianos G, Gitlin JD (2000) Semin Liver Dis 20:353–364

    Article  PubMed  CAS  Google Scholar 

  13. Gitlin JD (2003) Gastroenterology 125:1868–1877

    Article  PubMed  Google Scholar 

  14. Kitzberger R, Madl C, Ferenci P (2005) Metab Brain Dis 20:295–302

    Article  PubMed  Google Scholar 

  15. Bush AI (2003) Trends Neurosci 26:207–214

    Article  PubMed  CAS  Google Scholar 

  16. Bush AI (2000) Curr Opin Chem Biol 4:184–191

    Article  PubMed  CAS  Google Scholar 

  17. Gaggelli E, Kozlowski H, Valensin D, Valensin G (2006) Chem Rev 106:1995–2044

    Article  PubMed  CAS  Google Scholar 

  18. Barnham KJ, Bush AI (2008) Curr Opin Chem Biol 12:222–228

    Article  PubMed  CAS  Google Scholar 

  19. Macreadie IG (2008) Eur Biophys J Biophys Lett 37:295–300

    CAS  Google Scholar 

  20. Carrí MT, Ferri A, Cozzolino M, Calabrese L, Rotilio G (2003) Brain Res Bull 61:365–374

    Article  PubMed  CAS  Google Scholar 

  21. Wijesekera LC, Leigh PN (2009) Orphanet J Rare Dis 4:3

    Article  PubMed  Google Scholar 

  22. Rae TD, Schmidt PJ, Pufahl RA, Culotta VC, O’Halloran TV (1999) Science 284:805–808

    Article  PubMed  CAS  Google Scholar 

  23. Finney LA, O’Halloran TV (2003) Science 300:931–936

    Article  PubMed  CAS  Google Scholar 

  24. Waldron KJ, Rutherford JC, Ford D, Robinson NJ (2009) Nature 460:823–830

    Article  PubMed  CAS  Google Scholar 

  25. Elam JS, Thomas ST, Holloway SP, Taylor AB, Hart PJ (2002) Adv Protein Chem 60:151–219

    Article  PubMed  CAS  Google Scholar 

  26. Rosenzweig AC (2001) Acc Chem Res 34:119–128

    Article  PubMed  CAS  Google Scholar 

  27. Huffman DL, O’Halloran TV (2001) Annu Rev Biochem 70:677–701

    Article  PubMed  CAS  Google Scholar 

  28. O’Halloran TV, Culotta VC (2000) J Biol Chem 275:25057–25060

    Article  PubMed  Google Scholar 

  29. Luk E, Jensen LT, Culotta VC (2003) J Biol Inorg Chem 8:803–809

    Article  PubMed  CAS  Google Scholar 

  30. Culotta VC, Yang M, O’Halloran TV (2006) Biochim Biophys Acta Mol Cell Res 1763:747–758

    Article  CAS  Google Scholar 

  31. Rothstein JD, Becker M, Hoberg MD, Culotta V, Corson L, Cleveland D, Price D, Wong P (1998) Ann Neurol 44:7

    Article  Google Scholar 

  32. Abajian C, Yatsunyk LA, Ramirez BE, Rosenzweig AC (2004) J Biol Chem 279:53584–53592

    Article  PubMed  CAS  Google Scholar 

  33. Glerum DM, Shtanko A, Tzagoloff A (1996) J Biol Chem 271:14504–14509

    Article  PubMed  CAS  Google Scholar 

  34. Pierrel F, Cobine PA, Winge DR (2007) Biometals 20:675–682

    Article  PubMed  CAS  Google Scholar 

  35. Horng Y-C, Cobine PA, Maxfield AB, Carr HS, Winge DR (2004) J Biol Chem 279:35334–35340

    Article  PubMed  CAS  Google Scholar 

  36. Hamza I, Prohaska J, Gitlin JD (2003) Proc Natl Acad Sci USA 100:1215–1220

    Article  PubMed  CAS  Google Scholar 

  37. Hamza I, Faisst A, Prohaska J, Chen J, Gruss P, Gitlin JD (2001) Proc Natl Acad Sci USA 98:6848–6852

    Article  PubMed  CAS  Google Scholar 

  38. Pufahl RA, Singer CP, Peariso KL, Lin SJ, Schmidt PJ, Fahrni CJ, Culotta VC, Penner-Hahn JE, O’Halloran TV (1997) Science 278:853–856

    Article  PubMed  CAS  Google Scholar 

  39. Petris MJ, Mercer JFB, Culvenor JG, Lockhart P, Gleeson PA, Camakaris J (1996) EMBO J 15:6084–6095

    PubMed  CAS  Google Scholar 

  40. Herd SM, Camakaris J, Christofferson R, Wookey P, Danks DM (1987) Biochem J 247:341–347

    PubMed  CAS  Google Scholar 

  41. Lin SJ, Culotta VC (1995) Proc Natl Acad Sci USA 92:3784–3788

    Article  PubMed  CAS  Google Scholar 

  42. Itoh S, Kim HW, Nakagawa O, Ozumi K, Lessner SM, Aoki H, Akram K, McKinney RD, Ushio-Fukai M, Fukai T (2008) J Biol Chem 283:9157–9167

    Article  PubMed  CAS  Google Scholar 

  43. McRae R, Bagchi P, Sumalekshmy S, Fahrni CJ (2009) Chem Rev 109:4780–4827

    Article  PubMed  CAS  Google Scholar 

  44. Fahrni CJ (2007) Curr Opin Chem Biol 11:121–127

    Article  PubMed  CAS  Google Scholar 

  45. Lobinski R, Moulin C, Ortega R (2006) Biochimie 88:1591–1604

    Article  PubMed  CAS  Google Scholar 

  46. Ortega R, Devès G, Carmona A (2009) J R Soc Interface 6:S649–S658

    Article  PubMed  CAS  Google Scholar 

  47. Paunesku T, Vogt S, Maser J, Lai B, Woloschak G (2006) J Cell Biochem 99:1489–1502

    Article  PubMed  CAS  Google Scholar 

  48. Yang L, McRae R, Henary MM, Patel R, Lai B, Vogt S, Fahrni CJ (2005) Proc Natl Acad Sci USA 102:11179–11184

    Article  PubMed  CAS  Google Scholar 

  49. Finney L, Mandava S, Ursos L, Zhang W, Rodi D, Vogt S, Legnini D, Maser J, Ikpatt F, Olopade OI, Glesne D (2007) Proc Natl Acad Sci USA 104:2247–2252

    Article  PubMed  CAS  Google Scholar 

  50. Carmona A, Cloetens P, Devès G, Bohic S, Ortega R (2008) J Anal At Spectrom 23:1083–1088

    Article  CAS  Google Scholar 

  51. McRae R, Lai B, Vogt S, Fahrni CJ (2006) J Struct Biol 155:22–29

    Article  PubMed  CAS  Google Scholar 

  52. Vogt S (2003) J Phys IV 104:635–638

    Article  CAS  Google Scholar 

  53. Miyayama T, Suzuki KT, Ogra Y (2009) Toxicol Appl Pharmacol 237:205–213

    Article  PubMed  CAS  Google Scholar 

  54. La Fontaine S, Mercer JFB (2007) Arch Biochem Biophys 463:149–167

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Jonathan Gitlin (Washington University, St. Louis, USA) for providing us with samples of the Atox1−/− and Atox1+/+ cell lines. We also thank Stefan Vogt (Argonne National Laboratory) for providing support with the MAPS software package. Financial support from the National Institutes of Health (R01GM067169) is gratefully acknowledged. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357.

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Authors and Affiliations

  1. School of Chemistry and Biochemistry, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332, USA

    Reagan McRae & Christoph J. Fahrni

  2. X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, IL, 60439, USA

    Barry Lai

Authors
  1. Reagan McRae
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  2. Barry Lai
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  3. Christoph J. Fahrni
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Corresponding author

Correspondence to Christoph J. Fahrni.

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This article will be printed in the upcoming Journal of Biological Inorganic Chemistry special issue Cell Biology of Copper.

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McRae, R., Lai, B. & Fahrni, C.J. Copper redistribution in Atox1-deficient mouse fibroblast cells. J Biol Inorg Chem 15, 99–105 (2010). https://doi.org/10.1007/s00775-009-0598-1

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  • DOI: https://doi.org/10.1007/s00775-009-0598-1

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