Cadmium regulates copper homoeostasis by inhibiting the activity of Mac1, a transcriptional activator of the copper regulon, in Saccharomyces cerevisiae

Dong Hyuk Heo, In Joon Baek, Hyun Jun Kang, Ji Hyun Kim, Miwha Chang, Mi Young Jeong, Tae Hyoung Kim, Il Dong Choi, Cheol Won Yun

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11 Citations (Scopus)

Abstract

Cadmium is a toxic metal and the mechanism of its toxicity has been studied in various model systems from bacteria to mammals. We employed Saccharomyces cerevisiae as a model system to study cadmium toxicity at the molecular level because it has been used to identify the molecular mechanisms of toxicity found in higher organisms. cDNA microarray and Northern blot analyses revealed that cadmium salts inhibited the expression of genes related to copper metabolism. Western blotting, Northern blotting and chromatin immunoprecipitation experiments indicated that CTR1 expression was inhibited at the transcriptional level through direct inhibition of the Mac1 transcriptional activator. The decreased expression of CTR1 results in cellular copper deficiency and inhibition of Fet3 activity, which eventually impairs iron uptake. In this way, cadmium exhibits a negative effect on both iron and copper homoeostasis.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalBiochemical Journal
Volume431
Issue number2
DOIs
Publication statusPublished - 2010 Oct 15

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Keywords

  • Cadmium
  • Copper
  • Ctr1
  • Iron
  • Mac1
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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