Cited by 641Muscle Physiology and DisordersPI3K/AKT/mTOR signaling in cancerMuscle metabolism and nutrition

Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy

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Bentzinger, C. Florian, Romanino, Klaas, Cloëtta, Dimitri, Lin, Shuo, Mascarenhas, Joseph B., Oliveri, Filippo, Xia, Jinyu, Casanova, Emilio +5 more·2008·Cell Metabolism

Abstract

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.

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Registry

Crossref · 10.1016/j.cmet.2008.10.002

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  • Conditional deletion of mTOR with concomitant expression of catalytically inactive mTOR resulted in a growth rate defect starting after 1 week of age, and these mice show more severe muscle loss than conditional RAPTOR knockout.

    “Conditional deletion of mTOR with a concomitant expression of catalytically inactive mTOR, resulted in a growth rate defect that started after 1 week of age. Importantly, these mice show a more severe muscle loss when compared with the conditional RAPTOR knockout11.”
  • Muscle-specific Rictor knockout mice do not show any overt phenotype, whereas Raptor- and mTOR-deficient mice display reduced postnatal growth due to reduced size of fast but not slow muscle fibers and a progressive muscular dystrophy phenotype.

    “While muscle-specific Rictor knockout mice do not show any overt phenotype conversely, Raptor- and mTOR-deficient mice display reduced postnatal growth, due to the reduced size of fast but not slow muscle fibers and a progressive muscular dystrophy phenotype11,12.”
  • Deletion of the mTORC1 component raptor in mouse skeletal muscle affects PGC1α expression, reduces oxidative capacity, and induces premature ageing.

    “Deletion of the mTORC1 component raptor in mouse skeletal muscle affects PGC1α expression, reducing oxidative capacity36, and consequently inducing premature ageing.”
  • Muscle-specific knockout of Raptor causes muscular dystrophy in mice.

    “Knocking out the Raptor complex in adipose tissue enhances mitochondrial respiration244, but muscle-specific knockout causes muscular dystrophy in mice36.”

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Authors
Bentzinger, C. F., Romanino, K., Cloëtta, D., Lin, S., Mascarenhas, J. B., Oliveri, F., Xia, J., Casanova, E., Costa, C. F., Brink, M., Zorzato, F., Hall, M. N., & Rüegg, M. A.
Affiliations
  • University of Basel (CH)
  • University Hospital of Basel (CH)
Corresponding author
Rüegg, Markus A.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2008-11
Volume
8
Issue
5
Pages
411-424
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2016815316
Cited by
640
References
51
Citations by year
2026: 14 · 2025: 13 · 2024: 22 · 2023: 27 · 2022: 33 · 2021: 39 · 2020: 26 · 2019: 40 · 2018: 44 · 2017: 43 · 2016: 38 · 2015: 41 · 2014: 53 · 2013: 50 · 2012: 48
FWCI
14.66
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • edoc (University of Basel) (acceptedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
  • edoc (University of Basel)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
raptors, Rictor, mTORC1, mTORC2, skeletal muscle, muscular dystrophy, muscle metabolism, oxidative capacity, glycogen storage, mitochondrial biogenesis, PGC-1α, Akt signaling
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR, Rapamycin-Insensitive Companion of mTOR Protein, Animals, Carrier Proteins, Enzyme Activation, Gene Expression Regulation, Mitochondria, Muscular Dystrophies, Phosphorylation, Proteins, Transcription Factors, Trans-Activators, Mice, Knockout, Muscle, Skeletal, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Oncogene Protein v-akt, Mice, TOR Serine-Threonine Kinases

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