The effect and mechanism of aerobic exercise on mitochondrial structure and function in skeletal muscle of CAV-3 knockout mice

Long-term aerobic exercise training mitigates skeletal muscle mitochondrial dysfunction, and Caveolin-3 (CAV-3) is critical for mitochondrial homeostasis. However, whether aerobic exercise modulates mitochondrial structure and function through CAV-3 remains elusive. In this study, 40 mice (20 CAV-3 KO , 20 WT) were divided into 4 groups (NC, NE, KC, KE), Mice in the exercise group were trained to run at a certain pace for 5/days a week for 8 weeks. We examined the effects of aerobic exercise on skeletal muscle mitochondria in CAV-3 KO mice, thereby clarifying the role of CAV-3 in this process. First, we evaluated the exercise capacity and metabolic parameters of the mice, after training, the increase in their endurance was lower than that in WT mice, and there was no significant improvement in their metabolic parameters. Then, we observed changes in the morphology of mitochondrial cristae in skeletal muscle via transmission electron microscopy (TEM) and detected the expression levels of mitochondrial complexes I-V and OPA1 protein. The results showed that CAV-3 KO blocked the regulatory effect of aerobic exercise on mitochondrial cristae morphological parameters and the upregulation of mitochondrial complexes I-V and OPA1. Finally, at the molecular mechanism level, we verified that CAV-3 KO blocked the activation effect of aerobic exercise on the AKT/GSK-3β/PGC-1α signaling pathway. These findings provide evidence for the role of CAV-3 in maintaining mitochondrial homeostasis and reveal the potential mechanism by which aerobic exercise regulates mitochondrial function.