Redox proteomics

Abstract

In the presence of oxidative and nitrosative stress, proteins can undergo oxidative modification. A large variety of such modifications have been identified to date, including carbonylation, oxidation of aromatic amino acids, methionine sulfoxidation, and cysteine oxidation. While unintended oxidative modifications most often lead to the damage of the affected proteins, oxidative modifications also play important roles in cellular redox sensing. Classical redox sensor proteins use reversible oxidative modifications to change their activity in response to a changing redox environment. These redox sensors are the focus of oxidative stress research and have been identified in all three kingdoms of life. They are involved in a wide variety of cellular processes ranging from central energy metabolism over protein quality control to the regulation of the oxidative stress response. Proteomic methods have been used to globally monitor the oxidation state of these redox sensors and to identify novel redox sensitive proteins. These methods can help us in understanding redox regulation and the role of protein oxidation under physiological and pathological conditions. In this chapter, we will provide an overview of the different oxidation products of amino acid side chains in proteins, discuss examples of their physiological relevance and present a selection of global methods to identify them. We put an emphasis on quantitative proteomic methods that are able to identify targets of oxidative modifications down to the amino acid.