AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation

Haihong Zong, Jian Ming Ren, Lawrence H. Young, Marc Pypaert, James Mu, Morris J. Birnbaum, Gerald I. Shulman

Research output: Contribution to journalArticle

697 Citations (Scopus)

Abstract

Mitochondrial biogenesis is a critical adaptation to chronic energy deprivation, yet the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved fuel sensor, in mitochondrial biogenesis we studied transgenic mite expressing a dominant-negative mutant of AMPK in muscle (DN-AMPK). Both DN-AMPK and WT mice were treated with β-guanidinopropionic acid (GPA), a creatine analog, which led to similar reductions in the intramuscular ATP/AMP ratio and phosphocreatine concentrations. In WT mice, GPA treatment resulted in activation of muscle AMPK and mitochondrial biogenesis. However, the same GPA treatment in DN-AMPK mice had no effect on AMPK activity or mitochondrial content. Furthermore, AMPK inactivation abrogated GPA-induced increases in the expression of peroxisome proliferator-activated receptor γ coactivator 1α and calcium/calmodulin-dependent protein kinase IV (both master regulators of mitochondrial biogenesis). These data demonstrate that by sensing the energy status of the muscle cell, AMPK is a critical regulator involved in initiating mitochondrial biogenesis.

Original languageEnglish (US)
Pages (from-to)15983-15987
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number25
DOIs
StatePublished - Dec 10 2002
Externally publishedYes

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Adenylate Kinase
AMP-Activated Protein Kinases
Organelle Biogenesis
Skeletal Muscle
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Muscles
Peroxisome Proliferator-Activated Receptors
Phosphocreatine
Creatine
Mites
Adenosine Monophosphate
Muscle Cells
Adenosine Triphosphate
guanidinopropionic acid

Keywords

  • β-guanidinopropionic acid
  • Calcium/calmodulin-dependent protein kinase IV
  • MP-activated protein kinase
  • Peroxisome proliferator-activated γ receptor coactivator-1α

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. / Zong, Haihong; Ren, Jian Ming; Young, Lawrence H.; Pypaert, Marc; Mu, James; Birnbaum, Morris J.; Shulman, Gerald I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 25, 10.12.2002, p. 15983-15987.

Research output: Contribution to journalArticle

Zong, Haihong ; Ren, Jian Ming ; Young, Lawrence H. ; Pypaert, Marc ; Mu, James ; Birnbaum, Morris J. ; Shulman, Gerald I. / AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 25. pp. 15983-15987.
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