S-nitrosylation and S-glutathionylation: Lying at the forefront of redox dichotomy or a visible synergism?

Abstract

The discovery of novel oxidoreductases and their specific functional revelations as cellular disulfide reductants, S-denitrosylases, or S-deglutathionylases, alongside the well-established major redoxins/antioxidant systems comprising thioredoxin and glutaredoxin, enlarges the spectrum of redox players in the intracellular milieu as well as pushes us to stand at the crossroads concerning the choice of antioxidants that can serve the benefit of catalyzing their cognate protein/non-protein substrates with better efficiencies than the rest. The complexity is extended to exploring the redundancy amongst the redoxin systems and identifying their overlapping or unique substrate preferences to intervene with oxidative or nitrosative stress-induced reversible protein posttranslational modifications such as S-nitrosylation and S-glutathionylation. Contrary to popular expectations of reiterating the theoretical and evidence-based existence of these modifications, the current review aims to take the first leap in delineating the logical reasons behind the competing susceptibility of reactive cysteine thiols toward either or both redox modifications and their subsequent extent of stability in the presence of cellular reductants (thioredoxin, glutaredoxin, thioredoxin-like mimetic or lipoic acid, dihydrolipoic acid, and glutathione), thus rebuilding the underpinnings of a 'redox-interactome' that can further pave the way for the global mapping of ideal substrates exhibiting stringencies or synergism in the context of translational redox research.

Keywords: Oxidative/nitrosative stress; Oxidoreductases; Redox Biochemistry; Redundancy; S-glutathionylation; S-nitrosylation.