Identification of S-nitroso-CoA reductases that regulate protein S-nitrosylation

Coenzyme A (CoA) is a small-molecular-weight thiol that plays a central role in cellular metabolism. We have discovered a novel, phylogenetically conserved class of enzymes that reduce S-nitroso-CoA (SNO-CoA) and thereby regulate protein S-nitrosylation. These denitrosylases, identified as alcohol dehydrogenase 6 (Adh6) in yeast and aldo-keto reductase 1A1 in mammals, may be analogized to deacetylases, which regulate CoA-mediated protein acetylation. In yeast, Adh6 (previously without ascribed cellular function) regulates endogenous protein S-nitrosylation (heretofore unknown) including function-altering S-nitrosylation that impacts CoA-related metabolism. Thus, our findings establish a novel role for CoA in protein S-nitrosylation (operating through SNO-CoA), which is governed by specific enzymes. This mechanism may regulate the influence of nitric oxide on cellular metabolism in health and disease.