NO/redox-based signaling and nitrosative stress. Molecular recognition by cysteine-containing proteins is achieved either through the existence of single classes of thiols that are adapted to differentiate NO modification (S-nitrosylation) from oxidations (S-glutathionylation, S-S [intramolecular disulfide] and/or sulfur oxides [SO_x^–, where x is 1–3]) – exemplified in protein 1 – or through the presence of multiple classes of thiols, each adapted to recognize different redox-related molecules, including NO, GSNO, H₂O₂, O₂, and cellular redox potential (for protein 2, note that some classes of thiols may be functionally linked to others, exemplified in the pO₂-dependent oxidation of RyR thiols that promotes S-nitrosylation). In model 1, thiol oxidation would adversely impact nitrosylation signaling. In model 2, signal malfunction may result from altered amounts, timing, and/or the nature of RNS/ROS-based modifications. S, cysteine thiol; GSH/GSSG, glutathione/glutathione disulfide; pO₂, partial pressure of O₂.