The yeast cytosolic thioredoxins are involved in the regulation of methionine sulfoxide reductase A

Previously we have shown that the binding complex formation of methionine sulfoxide reductase A (msrA) promoter and calcium phospholipid binding protein (CPBP) enhances msrA transcription and expression. The msrA promoter-CPBP-binding complex (PmsrA-CPBP) formation was similar in Δtrx1,  Δtrx2, and Δtrx3 yeast strains and their control, with or without exposure to H2O2. In Δtrx1/Δtrx2 double mutant the PmsrA-CPBP was similar to its parent strain, following exposure to H2O2 for 30 min. However, a late-onset loss of PmsrA-CPBP binding activity occurred following exposure to H2O2 for 24 hours. Hence, it was inferred that both Trx1 and Trx2 are involved in the PmsrA-CPBP formation during prolonged oxidative stress conditions. In addition, the survival rate of the Δtrx1Δ/trx2 double mutant was ∼10% of its parent strain when exposed to H2O2. The MsrA activity was obliterated in Δtrx1/Δtrx2 and Δtrx1 strains and remained intact in the Δtrx2 and Δtrx3 strains. The msrA mRNA level in Δtrx1 was significantly reduced in comparison to that of its control, slightly reduced in Δtrx2, and unchanged in Δtrx3, respectively. It is suggested that under normal growth conditions Trx1 is essential for msrA transcription and activity. Moreover, following long-term oxidative stress conditions, Trx1 and Trx2 appear to promote PmsrA-CPBP-binding activity and cell survival.