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- Title
Endoplasmic reticulum is a major target of cadmium toxicity in yeast.
- Authors
Gardarin, Aurélie; Chédin, Stéphane; Lagniel, Gilles; Aude, Jean-Christophe; Godat, Emmanuel; Catty, Patrice; Labarre, Jean
- Abstract
Cadmium (Cd2+) 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 Cd2+ 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 (Δ ire1 and Δ hac1) unable to induce the UPR are hypersensitive to Cd2+, but not to arsenite and mercury. The full functionality of the pathways involved in ER stress response is required for Cd2+ tolerance. The data also suggest that Cd2+-induced ER stress and Cd2+ toxicity are a direct consequence of Cd2+ accumulation in the ER. Cd2+ does not inhibit disulfide bond formation but perturbs calcium metabolism. In particular, Cd2+ activates the calcium channel Cch1/Mid1, which also contributes to Cd2+ entry into the cell. The results reinforce the interest of using yeast as a cellular model to study toxicity mechanisms in eukaryotic cells.
- Subjects
ENDOPLASMIC reticulum; CADMIUM poisoning; YEAST; OXIDATIVE stress; APOPTOSIS; SACCHAROMYCES cerevisiae
- Publication
Molecular Microbiology, 2010, Vol 76, Issue 4, p1034
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/j.1365-2958.2010.07166.x