Protein denitrosylation: enzymatic mechanisms and cellular functions

Nat Rev Mol Cell Biol. 2009 Oct;10(10):721-32. doi: 10.1038/nrm2764. Epub 2009 Sep 9.


S-Nitrosylation, the redox-based modification of Cys thiol side chains by nitric oxide, is a common mechanism in signal transduction. Dysregulated S-nitrosylation contributes to a range of human pathologies. New roles for protein denitrosylation in regulating S-nitrosylation are being revealed. Recently, several denitrosylases - the enzymes that mediate Cys denitrosylation - have been discovered, of which two enzyme systems in particular, the S-nitrosoglutathione reductase and thioredoxin systems, have been shown to be physiologically relevant. These highly conserved enzymes regulate signalling through multiple classes of receptors and influence diverse cellular responses. In addition, they protect from nitrosative stress in microorganisms, mammals and plants, thereby exerting profound effects on host-microbe interactions and innate immunity.

Publication types

  • Review

MeSH terms

  • Aldehyde Oxidoreductases / metabolism*
  • Humans
  • Nitric Oxide / metabolism
  • Nitrosation
  • Oxidation-Reduction
  • Proteins / metabolism*
  • S-Nitrosoglutathione / metabolism
  • S-Nitrosothiols / metabolism
  • Signal Transduction
  • Thioredoxins / metabolism*


  • Proteins
  • S-Nitrosothiols
  • Nitric Oxide
  • Thioredoxins
  • S-Nitrosoglutathione
  • Aldehyde Oxidoreductases
  • formaldehyde dehydrogenase, glutathione-independent