Haochen Wang

The Popeye domain-containing protein 1 (Popdc1), also known as Bves, plays a crucial role in maintaining skeletal muscle homeostasis, with its variants leading to limb–girdle muscular dystrophy type R25. Skeletal muscles of patients with the homozygous missense variant of Bves exhibit impaired membrane trafficking, while skeletal muscle fibers in bves^S191F homozygous mutant zebrafish are significantly reduced and disorganized. However, the mechanism by which the absence of bves induces skeletal muscle atrophy remains unclear. In this study, we discovered a novel mechanism whereby bves deficiency drives skeletal muscle atrophy by disrupting mitochondrial structure and function. Our findings indicate that bves knockout leads to a significant decrease in zebrafish’s ability to swim, atrophy of skeletal muscle tissue, loss of cell membrane localization signals, and abnormalities in mitochondrial structure and function. After an 8-week intervention of regular aerobic exercise, the symptoms of skeletal muscle atrophy in bves knockout zebrafish were significantly alleviated, and the expression levels of genes and proteins related to mitochondrial were effectively rescued. These findings establish a connection between bves deficiency-induced disruption of mitochondrial structure and function and the onset and progression of skeletal muscle tissue atrophy symptoms, thereby laying a molecular foundation for exercise rehabilitation strategies in atrophic myopathy.