Author ORCID Identifier

https://orcid.org/0009-0009-7317-9746

Semester

Summer

Date of Graduation

2026

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Biology

Committee Chair

Jennifer Gallagher

Committee Member

Eric Horstick

Committee Member

Rita Rio

Committee Member

Daniel Panaccione

Committee Member

Joseph Lynch

Abstract

Glyphosate, the most widely used herbicide in the world, is an inhibitor of chorismate biosynthesis, the precursor of aromatic amino acids. The target of glyphosate is absent in animals, but findings reporting toxicity in model organisms without a known mechanism or target are increasing. Saccharomyces cerevisiae is a useful and versatile model for understanding molecular mechanisms of toxicity. In yeast, previous work has shown that the aspartate/glutamate permease Dip5 is the proposed transporter for glyphosate and that mitochondrial metabolism has been implicated in response to glyphosate toxicity. This dissertation aimed to identify the effects of glyphosate on mitochondrial function through mitochondrial phenotyping, as well as understand how glyphosate exposure affects the yeast metabolome. This dissertation further focused on assessing human glutamate transporters for their ability to transport glyphosate through expressing them in yeast. Our results show that glyphosate reduces oxygen consumption rate and alters yeast ability to grow under respiratory conditions. Metabolomic analysis also shows a generalized disruption of nitrogen metabolism, as well as glycolysis, glycogen and energy metabolism. Lastly, we show that expression of human glutamate transporters AGT1 and xCT increases sensitivity to glyphosate in wildtype and dip5 cells. The findings of this dissertation suggest that glyphosate induces cellular toxicity that extends beyond the shikimate pathway and highlight the need to investigate off-target interactions. By identifying potential transporters in humans, this dissertation also paves the way for future research in animal models and in particular tissue types in which the proposed glyphosate transporters are highly expressed.

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