Idebenone alleviates rotenone-induced mitochondrial dysfunction through mitophagy and mitochondrial biogenesis in muscle cells

Idebenone, a synthetic quinone analog of coenzyme Q10, is a well-characterized antioxidant with clinical applications in treating diseases associated with mitochondrial dysfunction. However, it remains unclear whether idebenone can mitigate rotenone-induced oxidative stress and mitochondrial dysfunction in muscle cells. In this study, exposure of C2C12 myoblasts to rotenone resulted in a significant increase in cell death, intracellular and mitochondrial Reactive Oxygen Species, and the activation of Mitophagy and Autophagy, as evidenced by altered expression levels of PINK1, PARKIN, and p62/SQSTM1. Additionally, elevated mitochondrial fission (measured by DRP1 and FIS1 expression) and a decrease in energy production (assessed via Seahorse analysis) were observed compared to untreated cells. The translocation of cytoplasmic DRP1 to the mitochondria was further demonstrated by its colocalization with TOM20. Remarkably, treatment with idebenone reversed these effects, and pharmacological inhibition of PGC1A abolished the protective effects of idebenone on mitochondrial biogenesis and function. Our findings suggest that idebenone ameliorates rotenone-induced Apoptosis, oxidative stress, and mitochondrial damage in C2C12 cells, supporting its potential therapeutic role in the treatment of skeletal muscle atrophy.

C2C12; Idebenone; Mitochondrial dysfunction; Oxidative stress; Rotenone.