Induction of endoplasmic reticulum stress by human cytosolic superoxide dismutase 1 in yeast cells

Ngoc Trang Nguyen; 木俣（石渡）, 有紀; 細見, 昭; 木俣, 行雄

doi:10.51094/jxiv.1505

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Ngoc Trang Nguyen 奈良先端科学技術大学院大学先端科学技術研究科
木俣（石渡）, 有紀奈良先端科学技術大学院大学先端科学技術研究科
細見, 昭信州大学総合理工学研究科
木俣, 行雄奈良先端科学技術大学院大学先端科学技術研究科 https://orcid.org/0000-0002-0942-5385 https://researchmap.jp/unfolded

DOI:

https://doi.org/10.51094/jxiv.1505

キーワード:

神経変性疾患、異常蛋白質応答、サッカロミセス・セレビジエ

抄録

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.

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酵母細胞におけるヒト細胞質スーパーオキシドジスムターゼ1による小胞体ストレス惹起