Cmk1 Activates Rds2 To Resist Low-pH Stress in Candida glabrata.

In , the transcription factor Rds2 has been previously characterized as a regulator of glycerophospholipid metabolism, playing a crucial role in the response to osmotic stress. Here, we report that Rds2 is also involved in the response to pH 2.0 stress. At pH 2.0, the deletion of led to reduced cell growth and survival, by 33% and 57%, respectively, compared with those of the wild-type strain. These adverse phenotypes resulted from the downregulation of genes related to energy metabolism in the Δ strain at pH 2.0, which led to a 34% reduction of the intracellular ATP content and a 24% decrease in membrane permeability. In contrast, the overexpression of rescued the growth defect of the Δ strain and increased cell survival at pH 2.0 by 17% compared with that of the wild-type strain, and this effect was accompanied by significant increases in ATP content and membrane permeability, by 42% and 19%, respectively. Furthermore, we found that the calcium/calmodulin-dependent protein kinase (CaMK) Cmk1 physically interacts with the PAS domain of Rds2, and Cmk1 is required for Rds2 activation and translocation from the cytoplasm to the nucleus under pH 2.0 stress. Moreover, Cmk1 is critical for Rds2 function in resistance to pH 2.0 stress, because cells of the strain with a disrupted Cmk1-Rds2 interaction exhibited impaired energy metabolism and membrane permeability at pH 2.0. Therefore, our results indicate that Cmk1 positively regulates Rds2 and suggest that they promote resistance to low-pH stress by enhancing energy metabolism and membrane permeability in An acidic environment is the main problem in the production of organic acids in The present study reports that the calcium/calmodulin-dependent protein kinase Cmk1 positively regulates Rds2 to increase intracellular ATP content, membrane permeability, and resistance to low-pH stress. Hence, the transcription factor Rds2 may be a potential target for improving the acid stress tolerance of during the fermentation of organic acids. The present study also establishes a new link between the calcium signaling pathway and energy metabolism.