Abstract
Reactive oxygen species (ROS) generated during cellular metabolism are toxic to cells. As a result, cells must be able to identify ROS as a stress signal and induce stress response pathways that protect cells from ROS toxicity. Recently, peroxiredoxin (Prx)-induced relays of disulfide bond formation have been identified in budding yeast, namely the disulfide bond formation of Yap1, a crucial transcription factor for oxidative stress response, by a specific Prx Gpx3 and by a major Prx Tsa1. Here, we show that an atypical-type Prx Ahp1 can act as a receptor for alkylhydroperoxides, resulting in activation of the Cad1 transcription factor that is homologous to Yap1. We demonstrate that Ahp1 is required for the formation of intermolecular Cad1 disulfide bond(s) in both an in vitro redox system and in cells treated with alkylhydroperoxide. Furthermore, we found that Cad1-dependent transcriptional activation of the HSP82 gene is dependent on Ahp1. Our results suggest that, although the Gpx3-Yap1 pathway contributes more strongly to resistance than the Ahp1-Cad1 pathway, the Ahp1-induced activation of Cad1 can function as a defense system against stress induced by alkylhydroperoxides, possibly including lipid peroxides. Thus, the Prx family of proteins have an important role in determining peroxide response signals and in transmitting the signals to specific target proteins by inducing disulfide bond formation.
Highlights
Toxicity often arises from lipid peroxidation as well as production of alkoxyl/peroxyl radicals and aldehyde compounds, which are products of radical lipid reactions triggered by Reactive oxygen species (ROS)
We compared the requirement of GPX3, TSA1, and AHP1 genes for resistance to H2O2 and to the alkylhydroperoxide tBOOH (Fig. 1A)
TSA1 encodes a major Prx family protein; Tsa1 and Ahp1 consist of 91% and 3.9% of total Tpx, respectively [14, 21], and disruption of the TSA1 gene resulted in a modest increase in sensitivity to tBOOH and methyl linolenic acid
Summary
Toxicity often arises from lipid peroxidation as well as production of alkoxyl/peroxyl radicals and aldehyde compounds, which are products of radical lipid reactions triggered by ROS. The sulfenic acid rapidly forms a disulfide bond with Cys208, activating the transcription factor, which triggers expression of the target genes. The presence of H2O2 is first detected in yeast when a catalytic cysteine of Gpx is directly oxidized by H2O2 to form sulfenic acid This reaction is followed by the transient formation of an intermolecular disulfide bond with a cysteine residue in the Yap transcription factor. Whether molecular mechanisms other than those involving specific peroxide receptors participate in H2O2 sensing remains to be determined The fact that both Gpx and Tpx have thioredoxin (Trx)-dependent peroxidase (Tpx) activity is potentially important for developing a better understanding of H2O2 sensing. We addressed whether the Prx Ahp is responsible for hydroperoxide sensing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
