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- Title
Regulation of mitochondrial biogenesis in skeletal muscle by CaMK.
- Authors
Wu, Hai; Kanatous, Shane B; Thurmond, Frederick A; Gallardo, Teresa; Isotani, Eiji; Bassel-Duby, Rhonda; Williams, R Sanders
- Abstract
Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid metabolism and electron transport, and reduced susceptibility to fatigue during repetitive contractions. CaMK induced expression of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), a master regulator of mitochondrial biogenesis in vivo, and activated the PGC-1 gene promoter in cultured myocytes. Thus, a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells.
- Publication
Science (New York, N.Y.), 2002, Vol 296, Issue 5566, p349
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1071163