PMID- 19046572
OWN - NLM
STAT- MEDLINE
DCOM- 20090428
LR  - 20211203
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Linking)
VI  - 8
IP  - 5
DP  - 2008 Nov
TI  - Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic 
      changes and results in muscle dystrophy.
PG  - 411-24
LID - 10.1016/j.cmet.2008.10.002 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a central controller of cell growth. mTOR 
      assembles into two distinct multiprotein complexes called mTOR complex 1 (mTORC1) 
      and mTORC2. Here we show that the mTORC1 component raptor is critical for muscle 
      function and prolonged survival. In contrast, muscles lacking the mTORC2 
      component rictor are indistinguishable from wild-type controls. Raptor-deficient 
      muscles become progressively dystrophic, are impaired in their oxidative 
      capacity, and contain increased glycogen stores, but they express structural 
      components indicative of oxidative muscle fibers. Biochemical analysis indicates 
      that these changes are probably due to loss of activation of direct downstream 
      targets of mTORC1, downregulation of genes involved in mitochondrial biogenesis, 
      including PGC1alpha, and hyperactivation of PKB/Akt. Finally, we show that 
      activation of PKB/Akt does not require mTORC2. Together, these results 
      demonstrate that muscle mTORC1 has an unexpected role in the regulation of the 
      metabolic properties and that its function is essential for life.
FAU - Bentzinger, C Florian
AU  - Bentzinger CF
AD  - Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
FAU - Romanino, Klaas
AU  - Romanino K
FAU - Cloetta, Dimitri
AU  - Cloetta D
FAU - Lin, Shuo
AU  - Lin S
FAU - Mascarenhas, Joseph B
AU  - Mascarenhas JB
FAU - Oliveri, Filippo
AU  - Oliveri F
FAU - Xia, Jinyu
AU  - Xia J
FAU - Casanova, Emilio
AU  - Casanova E
FAU - Costa, Celine F
AU  - Costa CF
FAU - Brink, Marijke
AU  - Brink M
FAU - Zorzato, Francesco
AU  - Zorzato F
FAU - Hall, Michael N
AU  - Hall MN
FAU - Ruegg, Markus A
AU  - Ruegg MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Cell Metab. 2008 Nov;8(5):343-4. PMID: 19046565
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Carrier Proteins/genetics/*physiology
MH  - Enzyme Activation
MH  - Gene Expression Regulation
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/*physiology
MH  - Multiprotein Complexes
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - Muscular Dystrophies/*metabolism/pathology
MH  - Oncogene Protein v-akt/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Phosphorylation
MH  - Proteins
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Regulatory-Associated Protein of mTOR
MH  - TOR Serine-Threonine Kinases
MH  - Trans-Activators/metabolism
MH  - Transcription Factors/genetics/*physiology
EDAT- 2008/12/03 09:00
MHDA- 2009/04/29 09:00
CRDT- 2008/12/03 09:00
PHST- 2008/06/08 00:00 [received]
PHST- 2008/08/15 00:00 [revised]
PHST- 2008/10/07 00:00 [accepted]
PHST- 2008/12/03 09:00 [pubmed]
PHST- 2009/04/29 09:00 [medline]
PHST- 2008/12/03 09:00 [entrez]
AID - S1550-4131(08)00320-3 [pii]
AID - 10.1016/j.cmet.2008.10.002 [doi]
PST - ppublish
SO  - Cell Metab. 2008 Nov;8(5):411-24. doi: 10.1016/j.cmet.2008.10.002.