Mitochondrial fusion- and fission-related protein expression in the regulation of skeletal muscle mass.

Mitochondria in the skeletal muscle are essential for maintaining metabolic plasticity and function. Mitochondrial quality control encompasses the dynamics of the biogenesis and remodeling of mitochondria, characterized by the constant fission and fusion of mitochondria in response to metabolic stressors. However, the roles of mitochondrial fission or fusion in muscle hypertrophy and atrophy remain unclear. The aim of this study was to determine whether mitochondrial fusion and fission events are influenced by muscle hypertrophy or atrophy stimulation. Twenty-six male F344 rats were randomly assigned to a control group or were subjected to up to 14 days of either plantaris overload (via tenotomy of the gastrocnemius and soleus muscles; hypertrophy group) or hindlimb cast immobilization (atrophy group). After 14 days of treatment, plantaris muscle samples were collected to determine the expression levels of mitochondrial fusion- and fission-related proteins. Muscle weight and total muscle protein content increased following plantaris overload in the hypertrophy group, but decreased following immobilization for 14 days in the atrophy group. In the hypertrophied muscle, the level of activated dynamin-related protein 1 (Drp1), phosphorylated at Ser616, significantly increased by 25.8% (p = 0.014). Moreover, the protein expression level of mitochondrial fission factor significantly decreased by 36.5% in the hypertrophy group compared with that of the control group (p = 0.017). In contrast, total Drp1 level significantly decreased in the atrophied plantaris muscle (p = 0.011). Our data suggest that mitochondrial fission events may be influenced by both muscle hypertrophy and atrophy stimulation, and that mitochondrial fission- related protein Drp1 plays an important role in the regulation of skeletal muscle in response to mechanical stimulation.