The Role of NrF2 in Skeletal Muscle Phenotype and Mitochondrial Function

Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a master regulator of oxidative defence, by controlling the expression of a battery of antioxidant enzyme proteins during stressful stimuli. Although Nrf2 is widely expressed, its role in regulating skeletal muscle phenotype remains to be elucidated. We sought to investigate the impact of Nrf2 on exercise-induced mitochondrial adaptations and aging using wild-type (WT) and knockout (KO) mice at 3 and 12 months of age. Basally, our results indicate that Nrf2 is important for mitochondrial respiration and skeletal muscle performance. Although Nrf2 did not impact mitochondrial content under quiescent conditions, it was necessary for mitochondrial content adaptations that occur in response to training. However, we also showed that exercise was capable of rescuing the initial deficits in respiration and muscle performance in animals lacking Nrf2, highlighting the broad cellular signaling benefits of exercise training beneficial effects of exercise training.