Redox regulation of adaptive responses in skeletal muscle to contractile activity

Skeletal muscle is a highly malleable tissue that responds to changes in its pattern of activity or the mechanical and environmental stresses placed upon it. The signaling pathways involved in these multiple adaptations are increasingly well described, but there is a lack of information on the factors responsible for initiating these processes. Reactive oxygen species (ROS) are produced at various sites in skeletal muscle and there is increasing evidence that these species play targeted roles in modulating redox-sensitive signaling pathways that are important to the muscle for making adaptations. This review will outline some of the processes involved and the types of experimental approaches that seem necessary to fully evaluate these redox signaling systems in muscle. To understand how labile, highly reactive ROS can play a role in cell signaling that is discrete and yet regulated to prevent oxidative damage, an increased knowledge of the subcellular localization and compartmentalization of both ROS generation and the redox-sensitive targets of ROS activity is required. It seems likely that application of this increased knowledge will lead to new approaches to manipulating muscle metabolism to maintain health and prevent loss of muscle function in age-related diseases.