Emerging chemistry and biology in protein glutathionylation

Protein S-glutathionylation serves a regulatory role in proteins and modulates distinct biological processes implicated in health and diseases. Despite challenges in analyzing the dynamic and reversible nature of S-glutathionylation, recent chemical and biological methods have significantly advanced the field of S-glutathionylation, culminating in selective identification and detection, structural motif analysis, and functional studies of S-glutathionylation. This review will highlight emerging studies of protein glutathionylation, beginning by introducing biochemical tools that enable mass spectrometric identification and live-cell imaging of S-glutathionylation. Next, it will spotlight recent examples of S-glutathionylation regulating physiology and inflammation. Lastly, we will feature two emerging lines of glutathionylation research in cryptic cysteine glutathionylation and protein C-glutathionylation. [Display omitted] •Cysteine glutathionylation serves distinct regulatory roles in proteins.•Various biochemical tools have been developed for the identification, detection, and imaging of glutathionylation.•Proteomic strategies for site specific identification and site occupancy analyses of glutathionylation are available.•Functional analysis of glutathionylation spans all areas of human health, including cardiac regulation, and inflammation.•Evidence for cryptic cysteine glutathionylation and irreversible C-glutathionylation is emerging.