S-glutathionylation: indicator of cell stress and regulator of the unfolded protein response

Mol Interv. 2007 Dec;7(6):313-24. doi: 10.1124/mi.7.6.7.


The specific posttranslational modification of protein cysteine residues by the addition of the tripeptide glutathione is termed S-glutathionylation. This process is promoted by oxidative and nitrosative stress but also occurs in unstressed cells. Altered levels of S-glutathionylation in some proteins have been associated with numerous pathologies, many of which have been linked to redox stress in the endoplasmic reticulum (ER). Proper protein folding is dependent upon controlled redox conditions within the ER, and it seems that ER conditions can in turn affect rates of S-glutathionylation. This article seeks to bring together the ways through which these processes are interrelated and considers the implications of these interrelationships upon therapeutic approaches to disease.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Cysteine / chemistry
  • Cysteine / metabolism
  • Endoplasmic Reticulum / metabolism
  • Glutathione / chemistry
  • Glutathione / metabolism*
  • Glutathione Transferase / metabolism
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Oxidative Stress
  • Phosphorylation
  • Protein Disulfide-Isomerases / chemistry
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism
  • Protein Folding
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational
  • Signal Transduction


  • Glutathione Transferase
  • Protein Kinases
  • Protein Disulfide-Isomerases
  • Glutathione
  • Cysteine