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Exposure to the Methylselenol Precursor Dimethyldiselenide Induces a Reductive Endoplasmic Reticulum Stress in Saccharomyces cerevisiae
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 11, International Journal of Molecular Sciences, MDPI, 2021, 22 (11), pp.5467. ⟨10.3390/ijms22115467⟩, International Journal of Molecular Sciences, Vol 22, Iss 5467, p 5467 (2021), International Journal of Molecular Sciences, 2021, 22 (11), pp.5467. ⟨10.3390/ijms22115467⟩
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- Methylselenol (MeSeH) is a major cytotoxic metabolite of selenium, causing apoptosis in cancer cells through mechanisms that remain to be fully established. Previously, we demonstrated that, in Saccharomyces cerevisiae, MeSeH toxicity was mediated by its metabolization into selenomethionine by O-acetylhomoserine (OAH)-sulfhydrylase, an enzyme that is absent in higher eukaryotes. In this report, we used a mutant met17 yeast strain, devoid of OAH- sulfhydrylase activity, to identify alternative targets of MeSeH. Exposure to dimethyldiselenide (DMDSe), a direct precursor of MeSeH, caused an endoplasmic reticulum (ER) stress, as evidenced by increased expression of the ER chaperone Kar2p. Mutant strains (∆ire1 and ∆hac1) unable to activate the unfolded protein response were hypersensitive to MeSeH precursors but not to selenomethionine. In contrast, deletion of YAP1 or SKN7, required to activate the oxidative stress response, did not affect cell growth in the presence of DMDSe. ER maturation of newly synthesized carboxypeptidase Y was impaired, indicating that MeSeH/DMDSe caused protein misfolding in the ER. Exposure to DMDSe resulted in induction of the expression of the ER oxidoreductase Ero1p with concomitant reduction of its regulatory disulfide bonds. These results suggest that MeSeH disturbs protein folding in the ER by generating a reductive stress in this compartment.
- Subjects :
- QH301-705.5
[SDV]Life Sciences [q-bio]
Saccharomyces cerevisiae
Mutant
Catalysis
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Oxidoreductase
Physical and Theoretical Chemistry
Biology (General)
selenium
Molecular Biology
QD1-999
Spectroscopy
030304 developmental biology
YAP1
chemistry.chemical_classification
0303 health sciences
biology
Cell growth
Chemistry
Endoplasmic reticulum
Oxidative folding
disulfide bond formation
Organic Chemistry
reductive stress
General Medicine
unfolded protein response
biology.organism_classification
methylselenol
Computer Science Applications
Cell biology
[SDV] Life Sciences [q-bio]
dimethyldiselenide
oxidative folding
Unfolded protein response
ER stress
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 14220067 and 16616596
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....ce7de5ae8903881bd4b310d4594bd3ba
- Full Text :
- https://doi.org/10.3390/ijms22115467