Maximus Guorgui | 2025 I.S. Symposium

Name: Maximus Guorgui
Title: Exploring How a Mutant Form of Yeast Thioredoxin Reductase Trr1 Causes Growth Arrest
Major: Biochemistry and Molecular Biology
Advisor: James West

Thioredoxin reductase (Trr1) partners with thioredoxin (Trx) to protect against reactive oxygen species (ROS) and support deoxyribonucleotide biosynthesis. In yeast, Trr1 has two critical cysteines, C145 (catalytic) and C142 (resolving), which facilitate Trx reduction. Yeast lacking Trr1 exhibit growth arrest when overexpressing a C145A mutant of Trr1. This growth sensitivity is specific to strains lacking Trr1, as shown by testing different genetic backgrounds (wild-type, trr1Δ, trx1Δ trx2Δ, and trr1Δ trx1Δ trx2Δ) using a galactose-inducible system. Non-reducing SDS-PAGE analysis revealed high molecular weight (~70 kDa) bands in trr1-deficient yeast expressing either wild-type or C145A Trr1, suggesting the formation of disulfide-linked Trr1 homodimers. These findings imply that other conserved cysteines in Trr1, such as C142 or a semi-conserved C-terminal cysteine, may form non-productive complexes with unknown proteins. This raises the possibility of Trx-independent roles for Trr1 and related reductases. Further studies aim to identify these interactions and elucidate the mechanism behind the observed growth arrest.

Posted in Symposium 2025 on May 1, 2025.