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Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy
Open accessAbstract
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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“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.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [11]
In the citing paper
“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.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [11]
In the citing paper
“Deletion of the mTORC1 component raptor in mouse skeletal muscle affects PGC1α expression, reducing oxidative capacity36, and consequently inducing premature ageing.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [36]
In the citing paper
“Knocking out the Raptor complex in adipose tissue enhances mitochondrial respiration244, but muscle-specific knockout causes muscular dystrophy in mice36.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [36]
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Metadata
- 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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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
- Health Sciences › Nursing › Nutrition and Dietetics › 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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