The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
mTORC1 Controls Mitochondrial Activity and Biogenesis through 4E-BP-Dependent Translational Regulation
Open accessAbstract
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.
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“There are also in vitro data suggesting mTOR signaling enhances mitochondrial biogenesis (Morita et al., 2013).”
From Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities (2021) · cites this paper as Morita et al., 2013
In the citing paper
“Since mTORC1 and 4E-BP1 play important role in mitochondrial health (26,27), mitochondrial morphology using Transmission Electron Microscopy (TEM) was examined.”
From Enhanced mTORC1 signaling and Protein Synthesis in Parkinson’s Disease Pathogenesis Disease Pathogenesis (2022) · cites this paper as [27]
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Metadata
- Authors
- Morita, M., Gravel, S.-P., Chénard, V., Sikström, K., Zheng, L., Alain, T., Gandin, V., Avizonis, D., Arguello, M., Zakaria, C., McLaughlan, S., Nouet, Y., Pause, A., Pollak, M., Gottlieb, E., Larsson, O., St-Pierre, J., Topisirovic, I., & Sonenberg, N.
- Affiliations
- McGill University (CA)
- Karolinska Institutet (SE)
- Cancer Research UK (GB)
- Lady Davis Institute for Medical Research (CA)
- Corresponding author
- Sonenberg, Nahum
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 18
- Issue
- 5
- Pages
- 698-711
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2082564115
- Cited by
- 842
- References
- 66
- Citations by year
- 2026: 49 · 2025: 78 · 2024: 76 · 2023: 52 · 2022: 75 · 2021: 77 · 2020: 78 · 2019: 82 · 2018: 75 · 2017: 66 · 2016: 65 · 2015: 42 · 2014: 27
- FWCI
- 19.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-nd)
- Funders
- McGill University
- Canadian Institutes of Health Research (MOP115-195, 106603_1, CIHR MOP-7214)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mTORC1, 4E-BP, eIF4E-binding protein, mRNA translation, mitochondrial biogenesis, mitochondrial activity, oxidative phosphorylation, energy metabolism, translational regulation, ATP production, insulin resistance, cancer
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Adenosine Triphosphate, Animals, Autophagy, Cell Nucleus, DNA-Binding Proteins, DNA, Mitochondrial, Gene Expression Regulation, Humans, Mitochondria, Models, Biological, Phosphoproteins, RNA, Messenger, Transcription Factors, Protein Biosynthesis, Genome, Human, Cell Cycle Proteins, Cell Respiration, Ribosomal Protein S6 Kinases, Mitochondrial Proteins, Eukaryotic Initiation Factors, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases, Mitochondrial Turnover
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