Peroxiredoxins act as a post-translational modification in cytoplasmic protein quality control

The redox state of proteins is essential for their function and to guarantee cell fitness. In the endoplasmic reticulum, cells recognize and resolve undesirable cysteine oxidations by protein quality control machinery that involves protein disulfide isomerases. While disulfide bonds are uncommon in the reducing environment of the cytoplasm, they play a key role in redox signaling during oxidative stress and disease states. Using global proteomic analyses, here we show that the cytoplasmic peroxiredoxin Tsa1 covalently binds cysteine residues of hundreds of proteins, including metabolic enzymes, and acts as a protective chaperone to maintain protein function. Thioredoxins maintain the balance of this peroxiredoxin post-translational mark. Our study unveils a mechanism involving the peroxiredoxin-thioredoxin cycle in cytoplasmic protein quality control in eukaryotes