Exercise-Induced Skeletal Muscle Remodeling and Metabolic Adaptation: Redox Signaling and Role of Autophagy

Abstract

Significance: Skeletal muscle is a highly plastic tissue. Exercise evokes signaling pathways that strongly modify myofiber metabolism and physiological and contractile properties of skeletal muscle. Regular physical activity is beneficial for health and is highly recommended for the prevention of several chronic conditions. In this review, we have focused our attention on the pathways that are known to mediate physical training-induced plasticity. Recent Advances: An important role for redox signaling has recently been proposed in exercisemediated muscle remodeling and peroxisome proliferator-activated receptor c (PPARc) coactivator-1a (PGC1a) activation. Still more currently, autophagy has also been found to be involved in metabolic adaptation to exercise. Critical Issues: Both redox signaling and autophagy are processes with ambivalent effects; they can be detrimental and beneficial, depending on their delicate balance. As such, understanding their role in the chain of events induced by exercise and leading to skeletal muscle remodeling is a very complicated matter. Moreover, the study of the signaling induced by exercise is made even more difficult by the fact that exercise can be performed with several different modalities, with this having different repercussions on adaptation. Future Directions: Unraveling the complexity of the molecular signaling triggered by exercise on skeletal muscle is crucial in order to define the therapeutic potentiality of physical training and to identify new pharmacological compounds that are able to reproduce some beneficial effects of exercise. In evaluating the effect of new ''exercise mimetics,'' it will also be necessary to take into account the involvement of reactive oxygen species, reactive nitrogen species, and autophagy and their controversial effects. Antioxid. Redox Signal. 21, 154-176.

Redox Mechanism of Reactive Oxygen Species in Exercise

“…Moreover, increased ROS formation in active skeletal muscles plays a critical role in exercise adaptation by modulating muscle contraction (Mastaloudis et al, 2004; Radak et al, 2013). For example, endurance running is regarded as important for survival in human evolution since it can trigger exercise-associated adaptive responses through metabolic and redox challenges (Radak et al, 2013; Ferraro et al, 2014; Wiggs, 2015). However, contemporary lifestyles decrease physical activities and suppress human adaptive capacity of metabolism and redox homeostasis (Radak et al, 2013).…”

Redox regulation of autophagy in skeletal muscle

“…Indeed, autophagic flux has been shown to participate in pro-atrophic stimuli (11, 12, 82–90), fasting (91, 92), high fat diet/insulin resistance (93, 94), hypoxia (95), and exercise (9, 96–101). Conversely, impaired autophagy has been reported in several myopathies (23, 102–108).…”

Profiling Carbonylated Proteins in Heart and Skeletal Muscle Mitochondria from Trained and Untrained Mice

“…It must be underlined that this condition could be transient, since it has been demonstrated that the exercise-induced oxidative environment upregulates antioxidant enzymes and molecular chaperones 48 and that ROS production is essential for muscle adaptation. 45 In this study, we also identified the specific oxidation sites of proteins that resulted carbonylated in oxyblot experiments. It was reported that MCO is one of the most important causes of protein carbonylation in living cells.…”