Endoplasmic reticulum is a major target of cadmium toxicity in yeast

Mol Microbiol. 2010 May;76(4):1034-48. doi: 10.1111/j.1365-2958.2010.07166.x. Epub 2010 Apr 23.


Cadmium (Cd(2+)) is a very toxic metal that causes DNA damage, oxidative stress and apoptosis. Despite many studies, the cellular and molecular mechanisms underlying its high toxicity are not clearly understood. We show here that very low doses of Cd(2+) cause ER stress in Saccharomyces cerevisiae as evidenced by the induction of the unfolded protein response (UPR) and the splicing of HAC1 mRNA. Furthermore, mutant strains (Delta ire1 and Delta hac1) unable to induce the UPR are hypersensitive to Cd(2+), but not to arsenite and mercury. The full functionality of the pathways involved in ER stress response is required for Cd(2+) tolerance. The data also suggest that Cd(2+)-induced ER stress and Cd(2+) toxicity are a direct consequence of Cd(2+) accumulation in the ER. Cd(2+) does not inhibit disulfide bond formation but perturbs calcium metabolism. In particular, Cd(2+) activates the calcium channel Cch1/Mid1, which also contributes to Cd(2+) entry into the cell. The results reinforce the interest of using yeast as a cellular model to study toxicity mechanisms in eukaryotic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadmium / metabolism
  • Cadmium / toxicity*
  • Calcium Channels / metabolism
  • Drug Resistance, Fungal
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism
  • Membrane Glycoproteins / agonists
  • Membrane Glycoproteins / metabolism
  • Protein Folding
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / agonists
  • Saccharomyces cerevisiae Proteins / metabolism
  • Stress, Physiological*


  • CCH1 protein, S cerevisiae
  • Calcium Channels
  • MID1 protein, S cerevisiae
  • Membrane Glycoproteins
  • Saccharomyces cerevisiae Proteins
  • Cadmium