Peroxiredoxin Ahp1 Acts as a Receptor for Alkylhydroperoxides to Induce Disulfide Bond Formation in the Cad1 Transcription Factor

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.

Rice ASR1 Protein with Reactive Oxygen Species Scavenging and Chaperone-like Activities Enhances Acquired Tolerance to Abiotic Stresses in Saccharomyces cerevisiae

“…These proteins were found to be involved in the metabolic pathway (Fba1p, Eno2p, Adh1p, Pgk1p, and Tpi1p), antioxidant system (Ahp1p), and protein folding (Ssb2p) (Supplementary Table S1). Ahp1p, a thiol specific peroxiredoxin, highly accumulated in TF cells in the presence of H 2 O 2 when compared to WT cells, reduces the sensitivity to hydroperoxides, which improves the redox homeostasis of yeast (Iwai et al, 2010). Under H 2 O 2 -induced oxidative conditions, metabolic enzymes such as enolase (Eno2), alcohol dehydrogenase (isoforms 1 and 2), phosphoglycerate mutase (Gpm or Pgk), triosephosphate isomerase (Tpi1p) and fructose-1,6-biphosphate aldolase (Fba1p), as well as Hsp70 molecular chaperones, were also upregulated in the in TF yeast cells relative to the WT cells.…”

Requirement of peroxiredoxin on the stationary phase of yeast cell growth

“…One difference between Tsa1 and Ahp1 in the peroxidase active state is oligomer formation: Tsa1 forms dimers and A. Western blotting of Ahp1 was performed as described previously (Iwai et al, 2010). Lysates were prepared from the indicated yeast cells.…”

Loss of Vacuolar H+-ATPase (V-ATPase) Activity in Yeast Generates an Iron Deprivation Signal That Is Moderated by Induction of the Peroxiredoxin TSA2

“…The thiol peroxidases, Gpx3p and Ahp1p, bind and regulate activities of the Yap1p and Cad1p transcription factors (62,63). Furthermore, recent work in Schizosaccharomyces pombe showed that the monothiol glutaredoxin, Grx4p, associates with and inhibits the activity of the iron-regulatory proteins Php2 and Fep1 in an iron-dependent manner (64,65).…”