Redox signalling and microRNA feedback in exercise-mediated skeletal muscle remodelling

Abstract

Exercise induces the acute generation of reactive oxygen species (ROS) in skeletal muscle, which can regulate a range of redox signalling pathways that determine the adaptive response to exercise. The redox environment can directly affect excitation contraction coupling, calcium handling and inflammation but also regulate key signalling pathways involved in mitochondrial quality control and proteostasis. Additionally, exercise-induced regulation of microRNAs (miRs) levels can provide a feedback mechanism to fine tune the adaptive response. Endogenous ROS produced during exercise arise from diverse sources including NADPH oxidases (NOX), mitochondria, xanthine oxidase (XO) and phospholipase A2 (PLA2). As high levels of ROS can potentially be damaging, there is a sophisticated, organelle-specific antioxidant network in skeletal muscle that includes superoxide dismutases (SODs), catalases (CATs), peroxiredoxins (PRDXs) and glutathione peroxidases (GPXs). Due to their abundance, location and catalytic activity, emerging evidence highlights the potential role of the PRDX family as central mediators in coordinating the redox signalling cascade as a result of increased ROS generation. Several exercise related miRs contain binding sites for redox sensitive and exercise associated transcription factors (TFs), moreover some miRs can target these TFs, providing a potential feedback mechanism to maintain cellular homeostasis following disruption of the redox environment. The interconnected roles of redox signalling and miRs are discussed in exercise-induced skeletal muscle adaptations. Furthermore, the therapeutic potential of targeting these interconnected pathways to mitigate muscle ageing and dysfunction, can provide valuable insights into strategies for optimising muscle health and enhancing healthspan.