PMID- 21799304
OWN - NLM
STAT- MEDLINE
DCOM- 20120203
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1551-4005 (Linking)
VI  - 10
IP  - 16
DP  - 2011 Aug 15
TI  - Antagonistic control of muscle cell size by AMPK and mTORC1.
PG  - 2640-6
AB  - Nutrition and physical activity have profound effects on skeletal muscle 
      metabolism and growth. Regulation of muscle mass depends on a thin balance 
      between growth-promoting and growth-suppressing factors. Over the past decade, 
      the mammalian target of rapamycin (mTOR) kinase has emerged as an essential 
      factor for muscle growth by mediating the anabolic response to nutrients, 
      insulin, insulin-like growth factors and resistance exercise. As opposed to the 
      mTOR signaling pathway, the AMP-activated protein kinase (AMPK) is switched on 
      during starvation and endurance exercise to upregulate energy-conserving 
      processes. Recent evidence indicates that mTORC1 (mTOR Complex 1) and AMPK 
      represent two antagonistic forces governing muscle adaption to nutrition, 
      starvation and growth stimulation. Animal knockout models with impaired mTORC1 
      signaling showed decreased muscle mass correlated with increased AMPK activation. 
      Interestingly, AMPK inhibition in p70S6K-deficient muscle cells restores cell 
      growth and sensitivity to nutrients. Conversely, muscle cells lacking AMPK have 
      increased mTORC1 activation with increased cell size and protein synthesis rate. 
      We also demonstrated that the hypertrophic action of MyrAkt is enhanced in 
      AMPK-deficient muscle, indicating that AMPK acts as a negative feedback control 
      to restrain muscle hypertrophy. Our recent results extend this notion by showing 
      that AMPKalpha1, but not AMPKalpha2, regulates muscle cell size through the control of 
      mTORC1 signaling. These results reveal the diverse functions of the two catalytic 
      isoforms of AMPK, with AMPKalpha1 playing a predominant role in the control of muscle 
      cell size and AMPKalpha2 mediating muscle metabolic adaptation. Thus, the crosstalk 
      between AMPK and mTORC1 signaling is a highly regulated way to control changes in 
      muscle growth and metabolic rate imposed by external cues.
FAU - Mounier, Remi
AU  - Mounier R
AD  - Inserm U1016, Centre National de la Recherche Scientifique (CNRS), UMR8104, 
      University Paris Descartes, Institut Cochin, Paris, France.
FAU - Lantier, Louise
AU  - Lantier L
FAU - Leclerc, Jocelyne
AU  - Leclerc J
FAU - Sotiropoulos, Athanassia
AU  - Sotiropoulos A
FAU - Foretz, Marc
AU  - Foretz M
FAU - Viollet, Benoit
AU  - Viollet B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110815
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Protein Subunits)
RN  - 0 (Proteins)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Animals
MH  - Cell Size/drug effects
MH  - Food
MH  - Gene Knockout Techniques
MH  - Humans
MH  - Hypertrophy/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Motor Activity
MH  - Multiprotein Complexes
MH  - Muscle Development
MH  - Muscles/*cytology/drug effects/*metabolism
MH  - Protein Subunits/metabolism
MH  - Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Ribonucleotides/pharmacology
MH  - Signal Transduction/drug effects/physiology
MH  - Sirolimus/pharmacology
MH  - Starvation
MH  - TOR Serine-Threonine Kinases
EDAT- 2011/07/30 06:00
MHDA- 2012/02/04 06:00
CRDT- 2011/07/30 06:00
PHST- 2011/07/30 06:00 [entrez]
PHST- 2011/07/30 06:00 [pubmed]
PHST- 2012/02/04 06:00 [medline]
AID - 17102 [pii]
AID - 10.4161/cc.10.16.17102 [doi]
PST - ppublish
SO  - Cell Cycle. 2011 Aug 15;10(16):2640-6. doi: 10.4161/cc.10.16.17102. Epub 2011 Aug 
      15.