The Role of p53 in Determining Mitochondrial Adaptations to Endurance Training in Skeletal Muscle

p53 plays an important role in regulating mitochondrial homeostasis. However, it is unknown whether p53 is required for the physiological and mitochondrial adaptations with exercise training. Furthermore, it is also unknown whether impairments in the absence of p53 are a result of its loss in skeletal muscle, or a secondary effect due to its deletion in alternative tissues. Thus, we investigated the role of p53 in regulating mitochondria both basally, and under the influence of exercise, by subjecting C57Bl/6J whole-body (WB) and muscle-specific p53 knockout (mKO) mice to a 6-week training program. Our results confirm that p53 is important for regulating mitochondrial content and function, as well as proteins within the autophagy and apoptosis pathways. Despite an increased proportion of phosphorylated p53 (Ser¹⁵) in the mitochondria, p53 is not required for training-induced adaptations in exercise capacity or mitochondrial content and function. In comparing mouse models, similar directional alterations were observed in basal and exercise-induced signaling modifications in WB and mKO mice, however the magnitude of change was less pronounced in the mKO mice. Our data suggest that p53 is required for basal mitochondrial maintenance in skeletal muscle, but is not required for the adaptive responses to exercise training.