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Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK
Hai Wu,1Shane B. Kanatous,1Frederick A. Thurmond,1Teresa Gallardo,1Eiji Isotani,2Rhonda Bassel-Duby,1R. Sanders Williams3*
Endurance exercise training promotes mitochondrial biogenesis
in skeletal muscle and enhances muscle oxidative capacity, butthe
signaling mechanisms involved are poorly understood. To investigatethis adaptive process, we generated transgenic mice that selectivelyexpress in skeletal muscle a constitutively active form of
calcium/calmodulin-dependentprotein kinase IV (CaMKIV*). Skeletal
muscles from these miceshowed augmented mitochondrial DNA replication
and mitochondrialbiogenesis, up-regulation of mitochondrial
enzymes involved infatty acid metabolism and electron transport, and
reduced susceptibilityto fatigue during repetitive contractions. CaMK
induced expressionof peroxisome proliferator-activated receptor 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
biogenesisin mammalian cells.
1 Departments of Internal Medicine and
Molecular Biology,
2 Department of Physiology,
University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3 Duke University Medical Center School of Medicine,
Durham, NC 27710, USA.
*
To whom correspondence should be addressed. E-mail:
rswilliams{at}mc.duke.edu
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Regulation of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha ) and mitochondrial function by MEF2 and HDAC5.
M. P. Czubryt, J. McAnally, G. I. Fishman, and E. N. Olson (2003)
PNAS
100, 1711-1716
|Abstract »|Full Text »|PDF »
Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide.
E. Nisoli, E. Clementi, C. Paolucci, V. Cozzi, C. Tonello, C. Sciorati, R. Bracale, A. Valerio, M. Francolini, S. Moncada, et al. (2003)
Science
299, 896-899
|Abstract »|Full Text »|PDF »
Exercise induces transient transcriptional activation of the PGC-1{alpha} gene in human skeletal muscle.
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.
