Candida glabrata Med3 plays a role in altering cell size and budding index to coordinate cell growth
Candida glabrata Med3 plays a role in altering cell size and budding index to coordinate cell growth
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光滑念珠菌 Med3 在改变细胞大小和出芽指数以协调细胞生长方面发挥作用
DOI：
10.1128/aem.00781-18
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发表时间：
2018
影响因子：
4.4
通讯作者：
Liu Liming
中科院分区：
文献类型：
--
作者：
Liu Hui;Kong Lulin;Qi Yanli;Chen Xiulai;Liu Liming
本研究表明，CgMed3AB可以通过协调细胞乙酰辅酶A代谢和细胞周期蛋白CgCln3的动态平衡来调节光肩星天牛的细胞生长。具体地说，我们报道了CgMed3AB调节细胞乙酰-CoA水平，从而诱导Cgcln3的转录，最终导致细胞大小和发芽指数的变化。总之，我们报告了CgMed3AB作为一个车轮的功能，负责驱动细胞的乙酰-CoA代谢，间接诱导Cgcln3的转录，并协调细胞的生长。我们认为，介体亚单位可能是调节光肩星天牛细胞生长的重要调控靶点。摘要光滑假丝酵母是一种很有前途的有机酸产生菌。在这里，我们报告了缺失和定量表达的方法，以阐明光肩星毛藻Med3AB(CgMed3AB)，中介转录共激活因子的一个亚单位，在调节细胞生长中的作用。根据生长曲线图，CgMed3AB的缺失导致最终生物量下降8.6%，细胞存活率下降10.5%。根据转录组学数据，这种生长缺陷的原因可归因于涉及丙酮酸和乙酰辅酶A(CoA)相关代谢的基因在Cgmed3abΔ株中的表达变化。此外，删除Cgmed3ab后，乙酰辅酶A合成酶的mRNA水平下调，导致乙酰辅酶A合成酶和细胞乙酰辅酶A的活性分别降低22.8%和21%。此外，CgCln3的表达依赖于乙酰辅酶A，在该菌株中，CgCln3的mRNA水平降低了34%。结果，Cgmed3abΔ菌株的细胞大小和出芽指数都减小了。相反，与野生型细胞相比，过表达Cgmed3ab导致乙酰辅酶A增加16.8%，CgCln3mRNA水平增加120%，细胞大小增加19.1%，萌发指数增加13.3%。综上所述，这些结果表明，CgMed3AB通过协调细胞乙酰辅酶A和CgCln3之间的动态平衡来调节光肩星天牛的细胞生长。重要性本研究证明CgMed3AB可以通过协调细胞乙酰-辅酶A代谢和细胞周期蛋白CgCln3的动态平衡来调节光肩星天牛的细胞生长。具体地说，我们报道了CgMed3AB调节细胞乙酰-CoA水平，从而诱导Cgcln3的转录，最终导致细胞大小和发芽指数的变化。总之，我们报告了CgMed3AB作为一个车轮的功能，负责驱动细胞的乙酰-CoA代谢，间接诱导Cgcln3的转录，并协调细胞的生长。我们认为，介体亚单位可能是调节光肩星天牛细胞生长的重要调控靶点。
This study demonstrates that CgMed3AB can regulate cell growth in C. glabrata by coordinating the homeostasis of cellular acetyl-CoA metabolism and the cell cycle cyclin CgCln3. Specifically, we report that CgMed3AB regulates the cellular acetyl-CoA level, which induces the transcription of Cgcln3, finally resulting in alterations to the cell size and budding index. In conclusion, we report that CgMed3AB functions as a wheel responsible for driving cellular acetyl-CoA metabolism, indirectly inducing the transcription of Cgcln3 and coordinating cell growth. We propose that Mediator subunits may represent a vital regulatory target modulating cell growth in C. glabrata. ABSTRACT Candida glabrata is a promising microorganism for the production of organic acids. Here, we report deletion and quantitative-expression approaches to elucidate the role of C. glabrata Med3AB (CgMed3AB), a subunit of the mediator transcriptional coactivator, in regulating cell growth. Deletion of CgMed3AB caused an 8.6% decrease in final biomass based on growth curve plots and 10.5% lower cell viability. Based on transcriptomics data, the reason for this growth defect was attributable to changes in expression of genes involved in pyruvate and acetyl-coenzyme A (CoA)-related metabolism in a Cgmed3abΔ strain. Furthermore, the mRNA level of acetyl-CoA synthetase was downregulated after deleting Cgmed3ab, resulting in 22.8% and 21% lower activity of acetyl-CoA synthetase and cellular acetyl-CoA, respectively. Additionally, the mRNA level of CgCln3, whose expression depends on acetyl-CoA, was 34% lower in this strain. As a consequence, the cell size and budding index in the Cgmed3abΔ strain were both reduced. Conversely, overexpression of Cgmed3ab led to 16.8% more acetyl-CoA and 120% higher CgCln3 mRNA levels, as well as 19.1% larger cell size and a 13.3% higher budding index than in wild-type cells. Taken together, these results suggest that CgMed3AB regulates cell growth in C. glabrata by coordinating homeostasis between cellular acetyl-CoA and CgCln3. IMPORTANCE This study demonstrates that CgMed3AB can regulate cell growth in C. glabrata by coordinating the homeostasis of cellular acetyl-CoA metabolism and the cell cycle cyclin CgCln3. Specifically, we report that CgMed3AB regulates the cellular acetyl-CoA level, which induces the transcription of Cgcln3, finally resulting in alterations to the cell size and budding index. In conclusion, we report that CgMed3AB functions as a wheel responsible for driving cellular acetyl-CoA metabolism, indirectly inducing the transcription of Cgcln3 and coordinating cell growth. We propose that Mediator subunits may represent a vital regulatory target modulating cell growth in C. glabrata.