Exercise-induced metabolic response of supersulfides in skeletal muscle

Maintenance of appropriate redox status contributes to homeostasis in skeletal muscle function. Exercise enhances the antioxidant system of skeletal muscles; however, precise molecular mechanisms pertaining to this remain unclear. Growing evidence suggests that supersulfides play a major role in antioxidant and anti-inflammatory systems. Therefore, this study examined the exercise-induced metabolic responses of supersulfides in skeletal muscles. Ten-week-old male mice were assigned into either a sedentary and exercise group for two sets of tests: (1) a single-bout exercise and (2) a four-week training program. The expression of the supersulfide-synthesizing enzyme cysteinyl-tRNA synthetase 2 (CARS2) and GSSSH levels were higher in the single-bout exercise group compared to the sedentary group, whereas GSSSG levels were lower in the single-bout exercise group. The training group showed higher levels of CARS2 expression, sulfide ions, cysteine, and GSSG compared to the sedentary group. In addition, mitochondrial ATP synthase subunit α was identified as a persulfidated protein, and both its persulfidation and ATP synthase activity were increased after training. Furthermore, exercise interventions enhanced superoxide and hydrogen peroxide scavenging capacities. The findings suggest that both acute exercise and training modulate supersulfide metabolism in skeletal muscles, which may contribute to enhanced antioxidant and mitochondrial energy metabolism.