Jude Cerniglia | 2026 I.S. Symposium
Name: Jude Cerniglia
Title: Investigating the Roles of a Mitochondrial Thioredoxin in Baker鈥檚 Yeast Identified to Potentially Regulate Branched Chain Amino Acid Synthesis Enzymes
Majors: Biochemistry & Molecular Biology; Mathematics
Advisors: James West, Robert Kelvey
Oxidative stress is suspected to be a main contributor to aging and other diseases related to aging. One consequence of oxidative stress is the improper oxidation of thiols to form disulfides leading to protein dysfunction. Our lab is interested in how cells reduce disulfide bonds to combat the effects of protein oxidation. To maintain redox homeostasis and regulate disulfide formation, cells rely on compartmentalized thioredoxin and glutathione-glutaredoxin systems to reduce these disulfides. While most of these systems have been well studied, less is known about the mitochondrial thioredoxin system. Previous work identified that a mitochondrial thioredoxin in baker’s yeast, Trx3, interacts with enzymes involved in branched-chain amino acid (BCAA) synthesis, lysine synthesis, and the citric acid cycle. My project validated the formation of cross-linked complexes between Trx3 and key mitochondrial BCAA synthesis enzymes. Following up on these interactions, phenotypic assays revealed that disulfide reductase mutants lacking glutathione reductase and mitochondrial thioredoxin system proteins have an enhanced peroxide sensitivity on BCAA-deficient media. My research also found that the complete mitochondrial thioredoxin system knockout had a severe growth defect when grown on respiratory media. Due to Trx3’s diverse array of potential interaction partners, I expanded upon our biological results using an in silico approach via flux balance analysis. The model predicted compensatory metabolic shifts in enzymes such as Mae1 and Idp1 to maintain mitochondrial nicotinamide adenine dinucleotide (NAD) balance. These findings indicate that Trx3 could potentially function as a redox regulator for the citric acid cycle and BCAA synthesis.
Posted in Symposium 2026 on May 1, 2026.
