Candida glabrata Med3 Plays a Role in Altering Cell Size and Budding Index To Coordinate Cell Growth.

is a promising microorganism for the production of organic acids. Here, we report deletion and quantitative-expression approaches to elucidate the role of Med3AB (Med3AB), a subunit of the mediator transcriptional coactivator, in regulating cell growth. Deletion of Med3AB 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 Δ strain. Furthermore, the mRNA level of acetyl-CoA synthetase was downregulated after deleting , resulting in 22.8% and 21% lower activity of acetyl-CoA synthetase and cellular acetyl-CoA, respectively. Additionally, the mRNA level of Cln3, whose expression depends on acetyl-CoA, was 34% lower in this strain. As a consequence, the cell size and budding index in the Δ strain were both reduced. Conversely, overexpression of led to 16.8% more acetyl-CoA and 120% higher Cln3 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 Med3AB regulates cell growth in by coordinating homeostasis between cellular acetyl-CoA and Cln3. This study demonstrates that Med3AB can regulate cell growth in by coordinating the homeostasis of cellular acetyl-CoA metabolism and the cell cycle cyclin Cln3. Specifically, we report that Med3AB regulates the cellular acetyl-CoA level, which induces the transcription of , finally resulting in alterations to the cell size and budding index. In conclusion, we report that Med3AB functions as a wheel responsible for driving cellular acetyl-CoA metabolism, indirectly inducing the transcription of and coordinating cell growth. We propose that Mediator subunits may represent a vital regulatory target modulating cell growth in .