Yeast at the Crossroads: Nutrient Signalling Paths and Stressful Turns

Abstract

Nutrients serve essential functions as building blocks for cellular components. Intriguingly, they serve as signalling elements that control basic cellular functions. In microorganisms such as Saccharomyces cerevisiae, the availability of nutrients also comes along with further challenges such as fluctuations in osmolytes, oxygen levels, or pH. Adaptation to these factors requires a coordinated response from various cellular pathways to ensure survival. This thesis explores the intersection of nutrient signalling and osmotic stress responses in S. cerevisiae. Emphasis is placed on (I) the Snf1/Mig1 network, which regulates the response to carbon source availability, (II) the High Osmolarity Glycerol (HOG) pathway, governing the osmotic stress response (III) the transcriptional regulators Nrg1 and Nrg2, whose roles in coordinating nutrientand osmotic stress responses are not fully understood. Of particular interest in this study is how cells adapt to lithium ions. Lithium salts have also gained attention in aging research, yet despite their long history in mood disorder treatments, their exact effects on cellular signaling remain unclear. We found that low concentrations of glucose mitigate survival of yeast cells exposed to lithium chloride. While Nrg1/2 play distinct roles in the response to lithium chloride exposure, deleting NRG1 markedly increases growth rate in lithium chloride and glucose. Deletion of both genes confers phenotypic enhancement, resulting in a distinctive growth pattern with an initial surge and subsequent drop in growth. Separately, we found fluctuations in shuttling kinetics of Snf1 are influenced by the presence of non-fermentable carbon sources. Additionally, we employed a genome-wide genetic screen to link mitochondrial gene expression with nuclear genome regulation, offering new insights into the crosstalk between cellular subsystems. These findings contribute to our understanding of the complex crosstalk between nutrient signalling and osmotic stress responses. By shedding light on the regulatory processes involved in cellular adaptation, this research adds to our knowledge of how cells respond to environmental stressors. The implications of these mechanisms extend to broader biomedical contexts, including aging and age-related diseases such as metabolic disorders and cancer, where similar signalling pathways play a critical role.