Redox Modulation Matters: Emerging Functions for Glutaredoxins in Plant Development and Stress Responses

Abstract

Glutaredoxins (GRXs) are small ubiquitous glutathione (GSH)-dependent oxidoreductases that catalyze the reversible reduction of protein disulfide bridges or protein-GSH mixed disulfide bonds via a dithiol or monothiol mechanism, respectively. Three major classes of GRXs, with the CPYC-type, the CGFS-type or the CC-type active site, have been identified in many plant species. In spite of the well-characterized roles for GRXs in Escherichia coli, yeast and humans, the biological functions of plant GRXs have been largely enigmatic. The CPYC-type and CGFS-type GRXs exist in all organisms, from prokaryotes to eukaryotes, whereas the CC-type class has thus far been solely identified in land plants. Only the number of the CC-type GRXs has enlarged dramatically during the evolution of land plants, suggesting their participation in the formation of more complex plants adapted to life on land. A growing body of evidence indicates that plant GRXs are involved in numerous cellular pathways. In this review, emphasis is placed on the recently emerging functions for GRXs in floral organ development and disease resistance. Notably, CC-type GRXs have been recruited to participate in these two seemingly unrelated processes. Besides, the current knowledge of plant GRXs in the assembly and delivery of iron-sulfur clusters, oxidative stress responses and arsenic resistance is also presented. As GRXs require GSH as an electron donor to reduce their target proteins, GSH-related developmental processes, including the control of flowering time and the development of postembryonic roots and shoots, are further discussed. Profiling the thiol redox proteome using high-throughput proteomic approaches and measuring cellular redox changes with fluorescent redox biosensors will help to further unravel the redox-regulated physiological processes in plants.

Keywords: biotic and abiotic stresses; development; glutaredoxins (GRXs); glutathione (GSH); iron-sulfur clusters; redox regulation; thioredoxins (TRXs).

Figure 1

GRXs reduce disulfide bridges via a dithiol (A) or monothiol (B) mechanism. (A) Dithiol mechanism: electrons are transferred from NADPH to glutathione reductase (GR), then to glutathione (GSH) and further to glutaredoxin (GRX), eventually leading to the GRX-mediated reduction of disulfides in target proteins. (B) Monothiol mechanism: reduction of protein-GSH mixed disulfides is termed deglutathionylation (black arrows). The reverse reaction is called glutathionylation (gray arrows), resulting in the production of glutathionylated proteins. Adapted from [10].

Figure 2

Structural characterization of plant GRXs. (A) Ribbon representation of poplar GRXC1. Four central β-sheets are surrounded by five α-helices. The position of the conserved glycine in the GSH binding site is indicated in red, and the CGYC active site is blue. (B) Ribbon representation of Arabidopsis ROXY1 obtained by homology modeling using poplar GRXC1 as a template. The conserved glycine (G110, red) and the CCMC active site (blue) are respectively located on the same β-sheet and α-helix as in poplar GRXC1. Adapted from [7].

Figure 3

Oxidation and reduction of protein thiols. Under oxidative conditions, free and accessible protein thiols undergo several different posttranslational modifications, which can be either reversible or not. Protein cysteines can be oxidized by ROS into sulfenic acid (SOH), which can be reduced by XRX (GRX or TRX). Further oxidation of sulfenic acid by ROS can result in the formation of sulfinic acid (SO₂H), which can be reversed by sulfiredoxins (SRX) or irreversibly oxidized to sulfonic acid (SO₃H). The presence of oxidants and/or GSH allows the glutathionylation of protein cysteines to occur through different mechanisms. Deglutathionylation can be catalyzed by GRX. Reversible formation of intra-/inter-molecular disulfide bridges is mediated by XRX. Direct H₂O₂-dependent oxidation of cysteines to intra-/intermolecular disulfides and peroxidase (POX)-catalyzed H₂O₂ sensing can be reversed by XRX. Besides, protein cysteines also undergo nitrosylation in the presence of reactive nitrogen species (RNS), a reversible process that could be catalyzed by TRX. Adapted from [48].