The C57Bl/6 mouse serves as a suitable model of human skeletal muscle mitochondrial function

New Findings • What is the central question of this study?Do mouse skeletal muscle mitochondria resemble human skeletal muscle mitochondria sufficiently to serve as a proper model and how do differences of skeletal muscle type affect the comparison? • What is the main finding and its importance?We find that mouse skeletal muscle respiratory capacity and control function rather similar to human m. vastus lateralis, with the mouse quadricep being overall the most similar. This resemblance is not universal, however, because the coupling control of electron transport during fat oxidation in type I murine muscle is more comparable to human vastus lateralis. It is debatable whether differences in mitochondrial function exist across skeletal muscle types and whether mouse skeletal muscle mitochondrial function can serve as a valid model for human skeletal muscle mitochondrial function. The aims of this study were to compare and contrast three different mouse skeletal muscles and to identify the mouse muscle that most closely resembles human skeletal muscle respiratory capacity and control. Mouse quadriceps (QUADM), soleus (SOLM) and gastrocnemius (GASTM) skeletal muscles were obtained from 8- to 10-week-old healthy mice (n= 8), representing mixed, oxidative and glycolytic muscle, respectively. Skeletal muscle samples were also collected from young, active, healthy human subjects (n= 8) from the vastis lateralis (QUADH). High-resolution respirometry was used to examine mitochondrial function in all skeletal muscle samples, and mitochondrial content was quantified with citrate synthase activity. Mass-specific respiration was higher across all respiratory states in SOLM versus both GASTM and QUADH (P < 0.01). When controlling for mitochondrial content, however, SOLM respiration was lower than GASTM and QUADH (P < 0.05 and P < 0.01, respectively). When comparing respiratory capacity between mouse and human muscle, QUADM exhibited only one different respiratory state when compared with QUADH. These results demonstrate that qualitative differences in mitochondrial function exist between different mouse skeletal muscles types when respiratory capacity is normalized to mitochondrial content, and that skeletal muscle respiratory capacity in young, healthy QUADM does correspond well with that of young, healthy QUADH.