Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK

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 const...

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Published inScience (American Association for the Advancement of Science) Vol. 296; no. 5566; pp. 349 - 352
Main Authors Wu, Hai, Kanatous, Shane B., Thurmond, Frederick A., Gallardo, Teresa, Isotani, Eiji, Bassel-Duby, Rhonda, Williams, R. Sanders
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for the Advancement of Science 12.04.2002
American Association for the Advancement of Science
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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 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.
AbstractList 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.
Wu et al generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV. The study found that a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells.
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.
Audience Academic
Author Thurmond, Frederick A.
Bassel-Duby, Rhonda
Isotani, Eiji
Williams, R. Sanders
Gallardo, Teresa
Wu, Hai
Kanatous, Shane B.
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  givenname: Hai
  surname: Wu
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  givenname: Shane B.
  surname: Kanatous
  fullname: Kanatous, Shane B.
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  givenname: Frederick A.
  surname: Thurmond
  fullname: Thurmond, Frederick A.
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  surname: Gallardo
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  givenname: R. Sanders
  surname: Williams
  fullname: Williams, R. Sanders
BackLink http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14185312$$DView record in Pascal Francis
https://www.ncbi.nlm.nih.gov/pubmed/11951046$$D View this record in MEDLINE/PubMed
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Issue 5566
Keywords Physical exercise
calmodulin-dependent protein kinase
Enzyme
Transferases
Rodentia
Transgenic animal
Gene expression
Striated muscle
Vertebrata
Mitochondria
Regulation(control)
Mammalia
Mouse
DNA
Replication
Endurance
Oxidation
Ca
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Snippet Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved...
Wu et al generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV....
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SubjectTerms Animals
Biological and medical sciences
Blood
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cytochromes
DNA Replication
DNA, Mitochondrial - biosynthesis
Electron Transport
Enzymes
Fatty Acids - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Expression Profiling
Human beings
Humans
Lymphocytes
Mammals
Man
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria
Mitochondria, Muscle - enzymology
Mitochondria, Muscle - metabolism
Muscle Contraction
Muscle Fatigue
Muscle Fibers, Skeletal - ultrastructure
Muscle, Skeletal - enzymology
Muscle, Skeletal - metabolism
Muscle, Skeletal - ultrastructure
Muscles
Oligonucleotide Array Sequence Analysis
Physiological aspects
Promoter Regions, Genetic
Receptors
Signal Transduction
Skeletal muscle
Striated muscle
Striated muscle. Tendons
Transcription Factors - genetics
Transcription Factors - metabolism
Transgenes
Transgenic animals
Transgenic plants
Up-Regulation
Vertebrates: osteoarticular system, musculoskeletal system
Title Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK
URI https://www.jstor.org/stable/3076527
https://www.ncbi.nlm.nih.gov/pubmed/11951046
https://search.proquest.com/docview/18381106
https://search.proquest.com/docview/21159942
https://search.proquest.com/docview/36193756
https://search.proquest.com/docview/71600809
Volume 296
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