| First Author | Miura S | Year | 2006 |
| Journal | Am J Pathol | Volume | 169 |
| Issue | 4 | Pages | 1129-39 |
| PubMed ID | 17003473 | Mgi Jnum | J:113374 |
| Mgi Id | MGI:3665528 | Doi | 10.2353/ajpath.2006.060034 |
| Citation | Miura S, et al. (2006) Overexpression of peroxisome proliferator-activated receptor gamma co-activator-1alpha leads to muscle atrophy with depletion of ATP. Am J Pathol 169(4):1129-39 |
| abstractText | Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) is a key nuclear receptor co-activator for mitochondrial biogenesis. Here we report that overexpression of PGC-1alpha in skeletal muscles increased mitochondrial number and caused atrophy of skeletal muscle, especially type 2B fiber-rich muscles (gastrocnemius, quadriceps, and plantaris). Muscle atrophy became evident at 25 weeks of age, and a portion of the muscle was replaced by adipocytes. Mice showed increased energy expenditure and reduced body weight; thyroid hormone levels were normal. Mitochondria exhibited normal respiratory chain activity per mitochondrion; however, mitochondrial respiration was not inhibited by an ATP synthase inhibitor, oligomycin, clearly indicating that oxidative phosphorylation was uncoupled. Accordingly, ATP content in gastrocnemius was markedly reduced. A similar phenotype is observed in Luft's disease, a mitochondrial disorder that involves increased uncoupling of respiration and muscle atrophy. Our results indicate that overexpression of PGC-1alpha in skeletal muscle increases not only mitochondrial biogenesis but also uncoupling of respiration, resulting in muscle atrophy. |
