Discovery of the novel antioxidant function of coenzyme A highlights its protective role during cellular stress. Mammalian and Bacterial cells subjected to oxidative and metabolic stress show significant increase in the covalent modification of protein cysteine residues by coenzyme A. This reversible modification is termed protein CoAlation (Protein-S-SCoA), which plays a similar role to protein S-glutathionylation by preventing the irreversible oxidation of the thiol group of cysteine residues.
Using anti-coenzyme A antibody and liquid chromatography tandem mass spectrometry (LC-MS/MS) methodologies, more than 2,000 CoAlated proteins were identified from stressed mammalian and bacterial cells.  The majority of these proteins are involved in cellular metabolism and stress response. Different research studies have focused on deciphering the coenzyme A-mediated regulation of proteins. Upon protein CoAlation, inhibition of the catalytic activity of different proteins (e.g. metastasis suppressor NME1, peroxiredoxin 5, GAPDH, among others) is reported. To restore the protein's activity, antioxidant enzymes that reduce the disulfide bond between coenzyme A and the protein cysteine residue play an important role. This process is termed protein deCoAlation. So far, two bacterial proteins, Thioredoxin A and Thioredoxin-like protein (YtpP), are shown to deCoAlate proteins.