mTORC1 controls mitochondrial biogenesis and activity through 4E-BP-dependent translation.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Mammalian cells |
| Journal | Cell metabolism |
| Year | 2013 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cmet.2013.10.001 · PMID 24206664 |
mRNA translation is thought to be the most energy-consuming process in the cell. Translation and energy metabolism are dysregulated in a variety of diseases including cancer, diabetes, and heart disease. However, the mechanisms that coordinate translation and energy metabolism in mammals remain largely unknown. The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates mRNA translation and other anabolic processes. We demonstrate that mTORC1 controls mitochondrial activity and biogenesis by selectively promoting translation of nucleus-encoded mitochondria-related mRNAs via inhibition of the eukaryotic translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). Stimulating the translation of nucleus-encoded mitochondria-related mRNAs engenders an increase in ATP production capacity, a required energy source for translation. These findings establish a feed-forward loop that links mRNA translation to oxidative phosphorylation, thereby providing a key mechanism linking aberrant mTOR signaling to conditions of abnormal cellular energy metabolism such as neoplasia and insulin resistance.
| Intervention | Genetic/pharmacologic (mTORC1 / 4E-BP) |
| Target | mTORC1 / 4E-BP |
| Model | Mammalian cells |
| Effect | mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translation |