Quantitative Proteomic Approaches to Study Redox Post-Translational Modifications in Skeletal Muscle

Reactive oxygen species are essential signalling molecules that regulate numerous aspects of skeletal muscle physiology. These effects are mediated through redox post-translational modifications on protein cysteine thiols, which influence the structure and function of redox-sensitive proteins. Mass spectrometry–based redox proteomic approaches have greatly advanced our ability to detect and characterise cysteine redox modifications, revealing a broad network of redox-sensitive proteins and pathways in skeletal muscle. Recent methodological developments enable quantification of the stoichiometry of reversible oxidative modifications at specific cysteine residues, providing critical insight into the extent and functional relevance of site-specific redox regulation. Redox proteomic approaches are being employed to improve our understanding of the specific redox protein modifications underlying physiological and pathophysiological processes in skeletal muscle. This review summarises current proteomic strategies for quantifying redox post-translational modifications and their application to study redox signalling in skeletal muscle. Emerging experimental approaches that offer the potential to study the specific roles of site-specific redox modifications in muscle physiology are also discussed. Collectively, these technologies present exciting opportunities to define the mechanistic roles of individual cysteine residues in muscle biology and help uncover new therapeutic avenues for conditions characterised by impaired redox homeostasis.