Peroxiredoxin 3 has a Crucial Role in the Contractile Function of Skeletal Muscle via Regulating Mitochondrial Homeostasis

Antioxidant systems against reactive oxygen species (ROS) are the important factors to regulate homeostasis in various cells, tissues and organs. Although ROS are known to cause to muscular disorders,the effects of mitochondrial ROS in muscle physiology have not been fully understood.Here, we investigated the effect of ROS on muscle mass and function using mice deficient in peroxiredoxin 3 (Prx3), which is a mitochondrial antioxidant protein. Ablation of Prx3 deregulated mitochondrial network and membrane potential of myotubes, in which ROS levels were increased. We showed that DNA content of mitochondria and ATP production are also reduced in Prx3 KO muscle. Of note, the mitofusin 1 and 2 protein levels decreased in Prx3 KO muscle, a biochemical evidence of impaired mitochondrial fusion. Contractile dysfunction was examined by measuring isometric forces of isolated EDL and soleus muscles. Maximum absolute forces in both the EDL and soleus muscles were not significantly affected in Prx3 KO mice. However, fatigue trials revealed that the decrease in relative force was greater and more rapid in soleus from Prx3 KO compared to wild type mice. Taken together, these results suggest that Prx3 plays a crucial role in mitochondrial homeostasis and, thereby controls the contractile functions of skeletal muscle.