Adaptation of Skeletal Muscles to Contractile Activity of Varying Duration and Intensity: The Role of PGC-1α

Abstract

A large body of experimental data have shown that aerobic exercise of different duration, intensity, and pattern affect molecular mechanisms regulating mitochondrial biogenesis in skeletal muscles. This review focuses on the effects of exercise duration and intensity on the molecular mechanisms of mitochondrial biogenesis regulation in skeletal muscles, namely PGC-1α-dependent signaling. Studies of the effects of acute exercise and exercise training showed that an increase in the duration of aerobic exercise from 30 to 90 min does not provide additional stimuli to activate signaling pathways regulating post-translational modification of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and expression of the PGC-1α gene (PPARGC1A). Conversely, exercise intensity substantially affects mitochondrial biogenesis due to the increase in the recruitment of type II muscle fibers with accompanying pronounced metabolic shift leading to the activation of signaling cascades and expression of genes regulating mitochondrial biogenesis. Therefore, intermittent exercise, which recruits type II muscle fibers, is more efficient in the activation of mitochondrial biogenesis than work-matched continuous exercise. In skeletal muscle adapted to aerobic training, intensity-dependent activation of mitochondrial biogenesis after acute exercise is associated primarily with the AMP-activated protein kinase/PGC-1α pathway, expression of PGC-1α-regulated genes, and expression of PPARGC1A from the alternative (distal) inducible promoter regulated by the cAMP response element-binding protein 1-related transcription factors and their coactivators. Elucidation of the effects of duration and intensity of aerobic exercise on the PGC-1α-dependent and -independent mechanisms of mitochondrial biogenesis is important for treatment of patients with various metabolic disorders, as well as for optimization of training in athletes.