Unconventional myosin VI is involved in regulation of muscle energy metabolism
Year: 2025
Type: article
Abstract: 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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G5893517712, G7913592234
OpenAlex ID: W4413313444