Induction of endoplasmic reticulum stress by human cytosolic superoxide dismutase 1 in yeast cells
##article.authors##
- Ngoc Trang Nguyen Graduate School of Science and Technology, Nara Institute of Science and Technology
- Yuki Ishiwata-Kimata Graduate School of Science and Technology, Nara Institute of Science and Technology
- Akira Hosomi Graduate School of Science and Technology, Shinshu University
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Yukio Kimata
Graduate School of Science and Technology, Nara Institute of Science and Technology
https://orcid.org/0000-0002-0942-5385
https://researchmap.jp/unfolded
DOI:
https://doi.org/10.51094/jxiv.1505Keywords:
Neurodegenerative diseases, Unfolded protein response, Saccharomyces cerevisiaeAbstract
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress, which triggers a transcriptome shift known as the unfolded protein response (UPR) commonly in eukaryotic species. Nevertheless, in some neurodegenerative diseases, the UPR is somehow induced by aggregation of cytosolic pathogenic proteins. To address the UPR induction mechanism by human superoxide dismutase 1 (hSOD1), the aggregation of which causes amyotrophic lateral sclerosis, here we used yeast Saccharomyces cerevisiae as a simple model organism. Expression of hSOD1 or its mutant increased UPR levels in S. cerevisiae cells carrying a knockout mutation of the STE24 gene, which encodes an ER-located membrane-integral protein that digests cytosolic proteins aberrantly translocated to the ER. Our findings cumulatively indicate that SOD1 induces ER stress and UPR by disturbing protein and lipid-membrane homeostasis in and on the ER.
Conflicts of Interest Disclosure
All authors declare that they have no conflicts of interest associated with this manuscript.Downloads *Displays the aggregated results up to the previous day.
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Submitted: 2025-09-01 11:11:50 UTC
Published: 2025-09-02 09:56:24 UTC
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Ngoc Trang Nguyen
Yuki Ishiwata-Kimata
Akira Hosomi
Yukio Kimata
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