Intracellular pathways of copper trafficking in yeast and humans

Valeria L Culotta, Su Ju Lin, Paul Schmidt, Leo W J Klomp, Ruby Leah B Casareno, Jonathan Gitlin

Research output: Contribution to journalArticle

Abstract

In the bakers yeast S. cerevisiae, there at least four intracellular targets requiring copper ions- 1) Ccc2p and Fet3p in the secretory pathway (homologues to Menkes/Wilson proteins and ceruloplasmin); 2) cytochrome oxidase in the mitochondria; 3) copper transcription factors in the nucleus; and 4) Cu/Zn superoxide dismutase (SOD1) in the cytosol. We have discovered a small soluble copper carrier that specifically delivers copper ions to the secretory pathway. This 8.2 kDa factor known as Atx1p, exhibits striking homology to the MERp mercury carrier of bacteria and contains a single MTCXXC metal binding site also found in the Menkes/Wilson family of copper transporting ATPases: Our studies show that Atx1p is cytosolic and facilitates the delivery of copper ions from the cell surface copper transporter to Ccc2p and Fet3p in the secretory pathway; furthermore, it is not involved in the delivery of copper ions to the mitochondria, the nucleus or cytosolic SOD1, implicating specific signals directing Atx1p to the secretory pathway. Homologues to Atx1p have been found in invertebrates, plants and humans, and the human gene is abundantly expressed in all tissues. In addition to Atx1p, we have recently uncovered an additional metal trafficking protein that appears to specifically deliver copper ions to SOD1. Mutants in the corresponding gene (lys7) are defective for SOD1 activity, and are unable to incorporate copper into SOD1, while there is no obvious impairment in copper delivery to cytochrome oxidase or Fet3p. The encoded 27 kDa protein contains a single MHCXXC consensus copper binding sequence and close homologues have been identified in a wide array of eukaryotic species including humans.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalAdvances in Experimental Medicine and Biology
Volume448
StatePublished - 1999

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Yeast
Copper
Yeasts
Secretory Pathway
Ions
Mitochondria
Electron Transport Complex IV
Saccharomyces cerevisiae
Genes
Metals
Transcription Factor 3
Proteins
Ceruloplasmin
Protein Transport
Invertebrates
Sequence Homology
Mercury
Cytosol
Bacteria
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Culotta, V. L., Lin, S. J., Schmidt, P., Klomp, L. W. J., Casareno, R. L. B., & Gitlin, J. (1999). Intracellular pathways of copper trafficking in yeast and humans. Advances in Experimental Medicine and Biology, 448, 247-254.

Intracellular pathways of copper trafficking in yeast and humans. / Culotta, Valeria L; Lin, Su Ju; Schmidt, Paul; Klomp, Leo W J; Casareno, Ruby Leah B; Gitlin, Jonathan.

In: Advances in Experimental Medicine and Biology, Vol. 448, 1999, p. 247-254.

Research output: Contribution to journalArticle

Culotta, VL, Lin, SJ, Schmidt, P, Klomp, LWJ, Casareno, RLB & Gitlin, J 1999, 'Intracellular pathways of copper trafficking in yeast and humans', Advances in Experimental Medicine and Biology, vol. 448, pp. 247-254.
Culotta, Valeria L ; Lin, Su Ju ; Schmidt, Paul ; Klomp, Leo W J ; Casareno, Ruby Leah B ; Gitlin, Jonathan. / Intracellular pathways of copper trafficking in yeast and humans. In: Advances in Experimental Medicine and Biology. 1999 ; Vol. 448. pp. 247-254.
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