Mitophagy in Botulinum Toxin Type A-Induced Muscle Atrophy

Botulinum toxin type A (BTXA) is widely used in oral and maxillofacial surgery to treat masseter hypertrophy and bruxism, inducing transient masseter atrophy, but the underlying mechanisms remain unclear. Mitophagy, essential for muscle fiber homeostasis, plays a critical role in muscle atrophy. This study aims to investigate whether mitophagy mediates BTXA-induced masseter muscle atrophy.

Rats received BTXA injections into masseter for 2 and 8 weeks. Muscle fiber composition was assessed via histology and immunofluorescence. Mitophagy markers (LC3-II, p62, beclin-1, Tomm20) were quantified by western blot. Mitochondrial function was evaluated via ATP content and mitochondrial DNA (mtDNA) copy number.

BTXA injection led to transient masseter muscle atrophy. During this process, the proportion of type IIA muscle fibers significantly increased, while the proportion of type IIB fibers decreased. Additionally, at 2 weeks post-BTXA injection, the expression levels of LC3-II, p62, and beclin-1 were notably upregulated, whereas Tomm20 expression was downregulated. Furthermore, a significant reduction in ATP content and mtDNA copy number was observed at the same time point, indicating impaired mitochondrial function.

These findings suggest that mitophagy plays a crucial role in BTXA-induced masseter muscle atrophy, providing new insights into the mechanisms underlying BTXA treatment.