PATHOLOGICAL IMPACT OF REDOX POST-TRANSLATIONAL MODIFICATIONS.

Oxidative stress is involved in the development of several pathologies. The different reactive oxygen species produced during oxidative stress lead to redox post-translational modifications (PTM) on proteins. This review provides an overview of recent data on cysteine and methionine oxidation and protein carbonylation following oxidative stress in a pathological context. It depends on multiple factors including amino-acid environment, accessibility, physical and chemical properties, as well as protein structures. Thiols can undergo reversible oxidations and others that are irreversible. On the contrary, carbonylation represent irreversible PTM. To date, hundreds of proteins were shown to be modified by ROS and RNS. We reviewed recent advances in the impact of the redox-induced PTMs on protein functions and activity as well as its involvement in diseases development or treatment. The current 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 thiols of cysteine or methionine residues, 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 too.