Key result
Loss of myosin VI in skeletal muscle leads to impaired mitochondrial function, reduced ATP production, and a compensatory shift from glycolytic to oxidative fiber types accompanied by AMPK activation.
Why the study?
Mitochondria are essential for skeletal muscle metabolism, but the role of unconventional motor myosin VI in mitochondrial function and muscle metabolism remains to be explored.
Myosin VI is a novel regulator of metabolic processes and mitochondrial function in skeletal muscle.
Preclinical data leave open myosin VI as a therapeutic target in human muscle disorders; human studies required.
Mitochondria are essential for regulation of the metabolic state of skeletal muscle, making their structure and function crucial for muscle performance. Myosin VI (MVI), an unconventional minus-end-directed motor, is expressed in skeletal muscle and myogenic cells. To explore its role in mitochondrial function and muscle metabolism, we used MVI knockout mice ( Snell’s waltzer, SV ) and their heterozygous littermates. We analyzed muscle samples from newborn (P0) and adult mice (3- and 12-month-old) and found that both MVI mRNA and protein levels were highest in newborn muscles and decreased with age. MVI expression also varied by muscle type, being highest in the slow-twitch soleus muscle (SOL) of adult mice. Loss of MVI had the most significant effects on SOL, which contains the highest number of mitochondria compared to fast-twitch muscles. MVI loss resulted in reduced respiratory capacity and ATP production in myogenic cells, indicating impaired mitochondrial function. Furthermore, MVI deficiency caused a shift from glycolytic to oxidative fiber types, especially in SOL. We also observed increased phospho-AMPK levels in MVI-KO SOL across all time points, along with downregulation of the mTOR pathway and upregulation of proteins involved in lipolysis. These findings highlight MVI as a novel regulator of metabolic processes in skeletal muscle.
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Wojton et al. (2025) studied Myosin VI deficiency (n=115). Myosin VI knockout vs. Heterozygous littermates (WT) was evaluated on Mitochondrial function and ATP production. Loss of myosin VI in skeletal muscle leads to impaired mitochondrial function, reduced ATP production, and a compensatory shift from glycolytic to oxidative fiber types accompanied by AMPK activation.
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