Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan Universitygrid.258151.a, Wuxi, China.
Beijing Key Laboratory of the Innovative Development of Functional Staple and Nutritional Intervention for Chronic Diseases, China National Research Institute of Food and Fermentation Industries Co., Ltd., Beijing, China.
Microbiol Spectr. 2022 Aug 31;10(4):e0089722. doi: 10.1128/spectrum.00897-22. Epub 2022 Aug 4.
Cells of the budding yeast Saccharomyces cerevisiae form spores or stationary cells upon nutrient starvation. These quiescent cells are known to resume mitotic growth in response to nutrient signals, but the mechanism remains elusive. Here, we report that quiescent yeast cells are equipped with a negative regulatory mechanism which suppresses the commencement of mitotic growth. The regulatory process involves a glycolytic enzyme, triosephosphate isomerase (Tpi1), and its product, glyceraldehyde-3-phosphate (GAP). GAP serves as an inhibitory signaling molecule; indeed, the return to growth of spores or stationary cells is suppressed by the addition of GAP even in nutrient-rich growth media, though mitotic cells are not affected. Reciprocally, dormancy is abolished by heat treatment because of the heat sensitivity of Tpi1. For example, spores commence germination merely upon heat treatment, which indicates that the negative regulatory mechanism is actively required for spores to prevent premature germination. Stationary cells of Candida glabrata are also manipulated by heat and GAP, suggesting that the regulatory process is conserved in the pathogenic yeast. Our results suggest that, in quiescent cells, nutrient signals do not merely provoke a positive regulatory process to commence mitotic growth. Exit from the quiescent state in yeast cells is regulated by balancing between the positive and negative signaling pathways. Identifying the negative regulatory pathway would provide new insight into the regulation of the transition from the quiescent to the mitotic state. Clinically, quiescent cells are problematic because they are resistant to environmental stresses and antibiotics. Given that the quiescent state is modulated by manipulation of the negative regulatory mechanism, understanding this process is important not only for its biological interest but also as a potential target for antifungal treatment.
在营养饥饿的情况下，出芽酵母酿酒酵母的细胞会形成孢子或静止细胞。这些静止的细胞已知会对营养信号做出反应，重新开始有丝分裂生长，但机制仍不清楚。在这里，我们报告说，静止的酵母细胞配备了一种负调控机制，抑制有丝分裂生长的开始。调控过程涉及一种糖酵解酶，磷酸丙糖异构酶（Tpi1）及其产物 3-磷酸甘油醛（GAP）。GAP 作为一种抑制性信号分子；事实上，即使在营养丰富的生长培养基中，添加 GAP 也会抑制孢子或静止细胞的生长恢复，尽管有丝分裂细胞不受影响。相反，由于 Tpi1 的热敏感性，热疗会消除休眠。例如，孢子仅在热处理后就开始萌发，这表明负调控机制对于孢子防止过早萌发是主动需要的。光滑念珠菌的静止细胞也可以通过热和 GAP 进行操纵，这表明该调控过程在致病性酵母中是保守的。我们的结果表明，在静止细胞中，营养信号不仅引发有丝分裂生长的正调控过程。酵母细胞从静止状态退出受到正负信号通路之间平衡的调节。鉴定负调控途径将为从静止到有丝分裂状态的转变的调控提供新的见解。临床上，静止细胞是有问题的，因为它们对环境压力和抗生素具有抵抗力。鉴于负调控机制的操纵可以调节静止状态，了解这个过程不仅对其生物学意义很重要，而且对抗真菌治疗也是一个潜在的目标。
