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

被引：1

作者：

Yaguchi, Kan ^{[1
]}

Sato, Kimino ^{[1
]}

Yoshizawa, Koya ^{[1
]}

Mikami, Daisuke ^{[2
]}

Yuyama, Kohei ^{[2
]}

Igarashi, Yasuyuki ^{[2
]}

Banhegyi, Gabor ^{[3
]}

Margittai, Eva ^{[4
]}

Uehara, Ryota ^{[1
,5
]}

机构：

[1] Hokkaido Univ, Grad Sch Life Sci, Sapporo, Hokkaido, Japan

[2] Hokkaido Univ, Fac Adv Life Sci, Lipid Biofunct Sect, Sapporo, Hokkaido, Japan

[3] Semmelweis Univ, Inst Biochem & Mol Biol, Budapest, Hungary

[4] Semmelweis Univ, Inst Translat Med, Budapest, Hungary

[5] Hokkaido Univ, Fac Adv Life Sci, Sapporo, Hokkaido, Japan

来源：

CELL STRUCTURE AND FUNCTION | 2021年 / 46卷 / 01期

关键词：

haploid; ER stress; Mevalonate pathway; UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM; CHOLESTEROL; STRESS; FARNESYLATION; TRANSLATION; PRENYLATION; PROTEOLYSIS; INHIBITION; APOPTOSIS;

D O I：

10.1247/csf.20055

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1 / 9

页数：9

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