Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes

Abstract

Glutathione (GSH), a tripeptide composed of glycine, cysteine, and glutamic acid, is an abundant thiol found in a wide variety of cells, ranging from bacterial to mammalian cells. Adequate levels of GSH are essential for maintaining iron homeostasis. The ratio of oxidized/reduced GSH is strictly regulated in each organelle to maintain the cellular redox potential. Cellular redox imbalances cause defects in physiological activities, which can lead to various diseases. Although there are many reports regarding the cellular response to GSH depletion, studies on stress response to high levels of GSH are limited. Here, we performed genome-scale screening in the yeast Saccharomyces cerevisiae and identified RIM11, BMH1, and WHI2 as multicopy suppressors of the growth defect caused by GSH stress. The deletion strains of each gene were sensitive to GSH. We found that Rim11, a kinase important in the regulation of meiosis, was activated via autophosphorylation upon GSH stress in a glucose-rich medium. Furthermore, RNA-seq revealed that transcription of phospholipid biosynthetic genes was downregulated under GSH stress, and introduction of multiple copies of RIM11 counteracted this effect. These results demonstrate that S. cerevisiae copes with GSH stress via multiple stress-responsive pathways, including a part of the adaptive pathway to glucose limitation.

The yeast 14-3-3 proteins Bmh1 and Bmh2 regulate key signaling pathways

“…This study proposed the existence of a Ste20p-independent branch (Ste20p is a yeast p21-activated kinase) of this pathway involving adaptor protein Bem4p, whereas the Ste20p-dependent branch requires Bmh1/2 proteins. Moreover, a recent genome-scale screening in S. cerevisiae identified BMH1 among multicopy suppressors of the growth defect caused by glutathione stress ( Yasukawa et al, 2023 ).…”

Key enzymes involved in the utilization of fatty acids by Saccharomyces cerevisiae: a review

“…Phosphatidic acid (PA) is a central metabolite in the synthesis of PL ( Engelhardt et al, 2023 ), and a series of synthesis occurs in the endoplasmic reticulum. First, fatty acyl-CoA and glycerol-3-phosphate (Glyc-3-P) synthesized lysophosphatidic acid (LPA) through G3P acyltransferases encoded by SCT1 (GAT2) and GPT2 (GAT1) in the endoplasmic reticulum ( Yasukawa et al, 2023 ), and LPA and fatty acyl-CoA formed PA through the LPA acyltransferase Slc1p/Slc4p in the endoplasmic reticulum, and then formed cytidine diphosphate diacylglycerol (CDP-DAG). CDP-DAG is a precursor for the synthesis of PL, which forms PI, PS, PE, PC under the action of celluloalcohol ( Matos et al, 2023 ).…”