Thiol-based H2O2 signalling in microbial systems

Abstract

Cysteine residues, and in particular their thiolate groups, react not only with reactive oxygen species but also with electrophiles and with reactive nitrogen species. Thus, cysteine oxidation has often been linked to the toxic effects of some of these reactive molecules. However, thiol-based switches are common in protein sensors of antioxidant cascades, in both prokaryotic and eukaryotic organisms. We will describe here three redox sensors, the transcription factors OxyR, Yap1 and Pap1, which respond by disulfide bond formation to hydrogen peroxide stress, focusing specially on the differences among the three peroxide-sensing mechanisms.

Keywords: Cys oxidation; H2O2 sensor; OxyR; Pap1; S. pombe; Yap1.

Graphical abstract

Fig. 1

Scheme depicting the activation of OxyR, Yap1 and Pap1 upon H₂O₂ stress. Bacterial OxyR seems to respond directly to the oxidizing signal. The eukaryotic Yap1 and Pap1 transcription factors, however, do require the participation of upstream H₂O₂ sensors: the glutathione peroxidase Gpx3 and the peroxiredoxin Tpx1, respectively. See details in the text.

Fig. 2

Schematic representation of Pap1 activation by H₂O₂. Upon moderate levels of peroxide stress (0.2 mM in the culture media), Tpx1 mediates disulfide bond formation in Pap1, which hinders the nuclear export signal (NES). Nuclear accumulation of oxidized Pap1 triggers transcription of both antioxidant and drug resistance genes. The relative positions of the seven cysteines residues (C) in Pap1 are indicated.

Fig. 3

Scheme of the Tpx1 cycle. Upper panel: under aerobic growth conditions, reduced thioredoxin Trx1 breaks the intramolecular disulfide of Tpx1 by disulfide exchange leading to a transient intermediate Trx1-S-S-Tpx1 to finally release oxidized Trx1 and reduced Tpx1. Bottom panel: under mild oxidative stress, the Tpx1 cycle becomes saturated, reduced Trx1 is depleted and Pap1 acts as an alternative electron donor to Tpx1.