Physical exercise elicits UPRmt in the skeletal muscle: The role of c-Jun N-terminal kinase

Abstract

Objective: The mitochondrial unfolded protein response (UPR^mt) is an adaptive cellular response to stress to ensure mitochondrial proteostasis and function. Here we explore the capacity of physical exercise to induce UPR^mt in the skeletal muscle.

Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses.

Results: Firstly, RNA sequencing and Western blotting analysis revealed that an acute aerobic session stimulated several mitostress-related genes and protein content in muscle, including the UPR^mt markers. Conversely, using a large panel of isogenic strains of BXD mice, we identified that BXD73a and 73b strains displayed low levels of several UPR^mt-related genes in the skeletal muscle, and this genotypic feature was accompanied by body weight gain, lower locomotor activity, and aerobic capacity. Finally, we identified that c-Jun N-terminal kinase (JNK) activation was critical in exercise-induced UPR^mt in the skeletal muscle since pharmacological JNK pathway inhibition blunted exercise-induced UPR^mt markers in mice muscle.

Conclusion: Our findings provide new insights into how exercise triggers mitostress signals toward the oxidative capacity in the skeletal muscle.

Keywords: JNK; Mitochondria; Physical exercise; Skeletal muscle; UPR(mt).