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Hokkaido University Collection of Scholarly and Academic Papers >
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Mevalonate Pathway-mediated ER Homeostasis Is Required for Haploid Stability in Human Somatic Cells
| Title: | Mevalonate Pathway-mediated ER Homeostasis Is Required for Haploid Stability in Human Somatic Cells |
| Authors: | Yaguchi, Kan Browse this author | | Sato, Kimino Browse this author | | Yoshizawa, Koya Browse this author | | Mikami, Daisuke Browse this author | | Yuyama, Kohei Browse this author | | Igarashi, Yasuyuki Browse this author | | Banhegyi, Gabor Browse this author | | Margittai, Eva Browse this author | | Uehara, Ryota Browse this author →KAKEN DB |
| Keywords: | haploid | | ER stress | | Mevalonate pathway |
| Issue Date: | 14-Sep-2021 |
| Publisher: | 一般社団法人 日本細胞生物学会(Japan Society for Cell Biology) |
| Journal Title: | Cell structure and function |
| Volume: | 46 |
| Issue: | 1 |
| Start Page: | 1 |
| End Page: | 9 |
| Publisher DOI: | 10.1247/csf.20055 |
| Abstract: | The somatic haploidy is unstable in diplontic animals, but cellular processes determining haploid stability remain elusive. Here, we found that inhibition of mevalonate pathway by pitavastatin, a widely used cholesterol-lowering drug, drastically destabilized the haploid state in HAP1 cells. Interestingly, cholesterol supplementation did not restore haploid stability in pitavastatin-treated cells, and cholesterol inhibitor U18666A did not phenocopy haploid destabilization. These results ruled out the involvement of cholesterol in haploid stability. Besides cholesterol perturbation, pitavastatin induced endoplasmic reticulum (ER) stress, the suppression of which by a chemical chaperon significantly restored haploid stability in pitavastatin-treated cells. Our data demonstrate the involvement of the mevalonate pathway in the stability of the haploid state in human somatic cells through managing ER stress, highlighting a novel link between ploidy and ER homeostatic control. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82665 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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