Abstract
This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)–mediated pathway and discusses the role of PGC-1α in skeletal muscle atrophy caused by immobilization. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF-1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant–antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle-specific PGC-1α overexpression underline the importance of PGC-1α in atrophied skeletal muscle, demonstrate enhancement of the PGC-1α mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC-1α appears to play a protective role against atrophy-linked skeletal muscle deterioration.
Highlights
Mitochondria in skeletal muscle tissue experience rapid and characteristic changes as a consequence of manipulations of muscle use and environmental conditions.[1]
The peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) emerged as a key transcriptional coactivator, which has provided a mechanistic insight for understanding how nuclear regulatory pathways are coupled with the biogenesis of mitochondria, antioxidant defense, and inflammatory response in skeletal muscle
We further examined the redox-sensitive nature of PGC-1␣ signaling during acute sprinting exercise and reported that reducing ROS generation with allopurinol to inhibit xanthine oxidase (XO), the main ROS source of this type of exercise, attenuated PGC-1␣ expression and PGC-1␣–controlled signaling pathway and mitochondrial biogenesis (Fig. 2).[48]
Summary
This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor␥ coactivator-1␣ (PGC-1␣)–mediated pathway and discusses the role of PGC-1␣ in skeletal muscle atrophy caused by immobilization. PGC-1␣ is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF-1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC-1␣ regulates cellular oxidant–antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle-specific PGC-1␣ overexpression underline the importance of PGC-1␣ in atrophied skeletal muscle, demonstrate enhancement of the PGC-1␣ mitochondrial biogenic pathway, and reduced oxidative damage. PGC-1␣ appears to play a protective role against atrophylinked skeletal muscle deterioration
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