TY - JOUR
T1 - Regulation of mitochondrial biogenesis in skeletal muscle by caMK
AU - Wu, Hai
AU - Kanatous, Shane B.
AU - Thurmond, Frederick A.
AU - Gallardo, Teresa
AU - Isotani, Eiji
AU - Bassel-Duby, Rhonda
AU - Williams, R. Sanders
PY - 2002/4/12
Y1 - 2002/4/12
N2 - 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 γ 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.
AB - 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 γ 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.
UR - http://www.scopus.com/inward/record.url?scp=0037066459&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037066459&partnerID=8YFLogxK
U2 - 10.1126/science.1071163
DO - 10.1126/science.1071163
M3 - Article
C2 - 11951046
AN - SCOPUS:0037066459
SN - 0036-8075
VL - 296
SP - 349
EP - 352
JO - Science
JF - Science
IS - 5566
ER -