Regulation of mitochondrial biogenesis in skeletal muscle by CaMK.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wu, H; Kanatous, SB; Thurmond, FA; Gallardo, T; Isotani, E; Bassel-Duby, R; Williams, RS

Published Date

  • April 2002

Published In

Volume / Issue

  • 296 / 5566

Start / End Page

  • 349 - 352

PubMed ID

  • 11951046

Pubmed Central ID

  • 11951046

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1071163

Language

  • eng