Pathological Impact of Redox Post-Translational Modifications

Oxidative stress is involved in the development of several pathologies. The different reactive oxygen species (ROS) produced during oxidative stress are at the origin of redox post-translational modifications (PTMs) on proteins and impact nucleic acids and lipids. This review provides an overview of recent data on cysteine and methionine oxidation and protein carbonylation following oxidative stress in a pathological context. Oxidation, like nitration, is a selective process and not all proteins are impacted. It depends on multiple factors, including amino acid environment, accessibility, and physical and chemical properties, as well as protein structures. Thiols can undergo reversible oxidations and others that are irreversible. On the contrary, carbonylation represents irreversible PTM. To date, hundreds of proteins were shown to be modified by ROS and reactive nitrogen species (RNS). We reviewed recent advances in the impact of redox-induced PTMs on protein functions and activity, as well as its involvement in disease development or treatment. These data show a complex situation of the involvement of redox PTM on the function of targeted proteins. Many proteins can have their activity decreased by the oxidation of cysteine thiols or methionine S-methyl thioethers, while for other proteins, this oxidation will be activating. This complexity of redox PTM regulation suggests that a global antioxidant therapeutic approach, as often proposed, is unlikely to be effective. However, the specificity of the effect obtained by targeting a cysteine or methionine residue to be able to inactivate or activate a particular protein represents a major interest if it is possible to consider this targeting from a therapeutic point of view with our current pharmacological tools.