Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress

Protein S-glutathiolation, the reversible covalent addition of glutathione to cysteine residues on target proteins, is emerging as a candidate mechani sm by which both changes in the intracellular redox state and the generatio n of reactive oxygen and nitrogen species may be transduced into a function al response. This review will provide an introduction to the concepts of ox idative and nitrosative stress and outline the molecular mechanisms of prot ein regulation by oxidative and nitrosative thiol-group modifications. Spec ial attention will be paid to recently published work supporting a role for S-glutathiolation in stress signalling pathways and in the adaptive cellul ar response to oxidative and nitrosative stress. Finally, novel insights in to the molecular mechanisms of S-glutathiolation as well as methodological problems related to the interpretation of the biological relevance of this post-translational protein modification will be discussed.