Persulfides in Protein Protection: Uncovering a new Co-Translational Modification

Persulfides (R–SSH) are emerging as important natural protectors against oxidative damage, acting both as strong antioxidants and as regulators of protein behavior. Through a process called persulfidation, an extra sulfur atom is added to specific cysteine residues in proteins, shielding them from harmful oxidation and subtly tuning their activity, stability, and interactions. Traditionally, persulfidation was thought to occur only after proteins are made, as a post-translational modification. However, new findings suggest it can also happen co-translationally—while the protein is still being synthesized. This early addition of sulfur may influence how proteins fold, form disulfide bonds, and maintain their structure under stress. Understanding this newly discovered mechanism could reshape how we view protein folding, redox biology, and the broader role of sulfur chemistry in maintaining cellular health.