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Mevalonate Pathway-mediated ER Homeostasis Is Required for Haploid Stability in Human Somatic Cells

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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
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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