The architecture of redox microdomains: Cascading gradients and peroxiredoxins’ redox-oligomeric coupling integrate redox signaling and antioxidant protection

• DOI: 10.1016/j.redox.2023.103000
• Publication Date: 2023-12-21T02:24:24Z
• Authors: Matthew Griffith; Adérito Araújo; Rui Travasso; Armindo Salvador
• Keywords: Peroxiredoxin

In the cytosol of human cells under low oxidative loads, hydrogen peroxide is confined to microdomains around its supply sites, due fast consumption by peroxiredoxins. So are sulfenic and disulfide forms 2-Cys peroxiredoxins, according a previous theoretical analysis [Travasso et al., Redox Biology 15 (2017) 297]. Here, an extended reaction-diffusion model that for first time considers differential properties peroxiredoxins 1 2 thioredoxin redox cycle predicts important new aspects dynamics microdomains. The peroxiredoxin sulfenates disulfides more localized than corresponding forms, former peroxiredoxin's faster resolution step. also localized. As H2O2 rate (vsup) approaches then surpasses maximal thioredoxin/thioredoxin reductase system (V), these concentration gradients become shallower, vanish. At vsup determines concentrations gradient length scale, but as V, activity gains influence. A mobility dimers vs. reduced decamers enhances polarity cytosol: preferentially retained far from sources, attenuating local buildup. Substantial total protein both emerge conditions, sources even increases with vsup. Altogether, such induces functional polarization between source-proximal regions (redox microdomains) facilitate peroxiredoxin-mediated signaling distal maximize antioxidant protection.