Muscle-specific raptor loss (not rictor) causes dystrophy, showing mTORC1 is essential for muscle homeostasis.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse (muscle raptor/rictor KO) |
| Journal | Cell metabolism |
| Year | 2008 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cmet.2008.10.002 · PMID 19046572 |
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.
| Intervention | Genetic – muscle-specific raptor KO (and rictor KO) |
| Target | mTORC1 (raptor) vs mTORC2 (rictor) |
| Model | Mouse (muscle raptor/rictor KO) |
| Effect | Raptor loss (not rictor) causes progressive muscular dystrophy and metabolic changes – mTORC1 essential for muscle |