Methylglyoxal inhibits nuclear division through alterations in vacuolar morphology and accumulation of Atg18 on the vacuolar membrane in Saccharomyces cerevisiae
Methylglyoxal inhibits nuclear division through alterations in vacuolar morphology and accumulation of Atg18 on the vacuolar membrane in Saccharomyces cerevisiae
复制标题
甲基乙二醛通过改变酿酒酵母液泡形态和 Atg18 在液泡膜上的积累来抑制核分裂
DOI：
10.1038/s41598-020-70802-8
复制
发表时间：
2020
影响因子：
4.6
通讯作者：
Inoue Yoshiharu
中科院分区：
文献类型：
--
作者：
Nomura Wataru;Aoki Miho;Inoue Yoshiharu
甲基乙二醛（Methylglyoxal， MG）是糖酵解过程中产生的一种天然代谢物，它能抑制各种生物体内细胞的生长。我们最近报道了MG抑制酿酒酵母的核分裂。然而，MG阻断核分裂的机制尚不清楚。在这里，我们发现磷脂酰肌醇3,5-二磷酸（PtdIns(3,5)P2）水平的增加对于MG对核分裂的抑制作用至关重要，而PtdIns(3,5)P2效应物Atg18的缺失减轻了MG介导的抑制作用。先前，我们报道MG改变液泡形态为单一肿胀形式，PtdIns(3,5) p2积聚。MG对细胞核分裂的抑制作用也需要液泡形态的改变。已知的检查点机制，包括纺锤体组装检查点和形态检查点，不参与MG对核分裂的阻断。我们的研究结果表明，Atg18在液泡膜上的积累和液泡形态的改变是mg诱导的核分裂抑制所必需的。
Methylglyoxal (MG) is a natural metabolite derived from glycolysis, and it inhibits the growth of cells in all kinds of organisms. We recently reported that MG inhibits nuclear division inSaccharomyces cerevisiae. However, the mechanism by which MG blocks nuclear division remains unclear. Here, we show that increase in the levels of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is crucial for the inhibitory effects of MG on nuclear division, and the deletion of PtdIns(3,5)P2-effector Atg18 alleviated the MG-mediated inhibitory effects. Previously, we reported that MG altered morphology of the vacuole to a single swelling form, where PtdIns(3,5)P2accumulates. The changes in the vacuolar morphology were also needed by MG to exert its inhibitory effects on nuclear division. The known checkpoint machinery, including the spindle assembly checkpoint and morphological checkpoint, are not involved in the blockade of nuclear division by MG. Our results suggest that both the accumulation of Atg18 on the vacuolar membrane and alterations in vacuolar morphology are necessary for the MG-induced inhibition of nuclear division.