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Investigating starvation survival in Saccharomyces cerevisiae

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2025-09-05
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Abstract

The ability to sense, assimilate and metabolize nutrients is crucial for the survival of Saccharomyces cerevisiae. Nutrient sensing and signaling pathways enable cells to regulate nutrient metabolism and modulate growth proliferation and viability. Under starvation conditions, cells exhibit different physiological responses based on the nutrient that is limiting growth. Recent evidence suggests that components of the mitochondria, specifically the electron transport chain (ETC), also play a role in starvation survival. Here, I describe novel signaling roles of the electron transport chain in the context of starvation survival and glucose derepression. I show how yeast strains with a defective ETC are unable to survive starvation in minimal medium. Loss of function mutations in major nutrient sensing and signaling pathways including Ras/PKA, TOR and PP2A suppress this ETC starvation defect. I characterize a subset of these suppressor mutations further and provide evidence of potential mechanisms by which they exert their effect. In a related study, I demonstrate how glucose-repressed ETC mutants are unable to utilize galactose as a carbon source, a phenomenon I term Failure of Glucose Derepression (FGD). FGD displays a variable phenotype and was not strain-specific. I describe how incomplete localization of key proteins within the Snf1 pathway in glucose repressed galactose grown ETC mutants potentially cause FGD thus highlighting a signaling role of the ETC in glucose derepression. Additionally, I expand current knowledge on cellular response to auxotrophic starvations by characterizing a panel of amino acid auxotrophs subjected to starvation of the cognate amino acid. I demonstrate that other phenotypes associated with auxotrophic starvations such as residual glucose concentrations are limited to only a subset of auxotrophic strains and are not characteristic of auxotrophic starvations in general. Pleiotropic effects of certain auxotrophic strains stress the importance of considering unintended phenotypes when using auxotrophic strains. Together, the results presented here shed light on novel signaling roles of a metabolic pathway and highlight important phenotypes to consider when using auxotrophic strains. These results are highly relevant to studying aging and age-associated phenotypes.

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279 pages

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2023-08

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Keywords

auxotroph; electron transport chain; glucose signaling; nutrient sensing; Saccharomyces cerevisiae; starvation survival

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Committee Chair

Gibney, Patrick

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Lee, Siu
Fox, Thomas

Degree Discipline

Food Science and Technology

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Ph. D., Food Science and Technology

Degree Level

Doctor of Philosophy

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Government Document

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dissertation or thesis

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