Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, 611-0011, Japan.
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, 611-0011, Japan.
Sci Rep. 2020 Aug 17;10(1):13887. doi: 10.1038/s41598-020-70802-8.
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 in Saccharomyces 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)P) is crucial for the inhibitory effects of MG on nuclear division, and the deletion of PtdIns(3,5)P-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)P accumulates. 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.
甲基乙二醛 (MG) 是一种来源于糖酵解的天然代谢物，它能抑制各种生物细胞的生长。我们最近报道，MG 能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，我们表明，磷脂酰肌醇 3,5-二磷酸 (PtdIns(3,5)P) 水平的增加对于 MG 对核分裂的抑制作用至关重要，并且 PtdIns(3,5)P 效应物 Atg18 的缺失减轻了 MG 介导的抑制作用。此前，我们报道，MG 将液泡的形态改变为单一肿胀形式，其中 PtdIns(3,5)P 积累。液泡形态的变化也是 MG 对核分裂发挥抑制作用所必需的。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。我们的结果表明，Atg18 在液泡膜上的积累和液泡形态的改变对于 MG 诱导的核分裂抑制都是必需的。
