Biological rhythms regulate numerous functional processes within organisms, including the expression of peroxisome proliferator-activated receptor-y coactivator 1-a (PGC-1a), a potent regulator of mitochondrial biogenesis. Homozygous Clock mutant mice are characterized by arrhythmic and suppressed expression of circadian genes within skeletal muscle, including PGC-1a. The present study sought to investigate mitochondrial physiology within these mutant animals, and to assess their adaptability to a chronic voluntary endurance training protocol. Our results indicate that Clock mutant mice exhibit decreased mitochondrial content, and this contributes to exercise intolerance in these mutant animals. Interestingly, endurance training ameliorates the decrement in mitochondrial content, as well as restores exercise capacity to levels evident in the wildtype mice. Thus, a functional CLOCK protein is necessary for optimal mitochondrial physiology, however Clock mutant mice retain the ability to adapt to chronic exercise
