Cited by 842PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerAutophagy in Disease and Therapy

mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation

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Morita, Masahiro, Gravel, Simon-Pierre, Chénard, Valérie, Sikström, Kristina, Zheng, Liang, Alain, Tommy, Gandin, Valentina, Avizonis, Daina +11 more·2013·Cell Metabolism

Abstract

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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Crossref · 10.1016/j.cmet.2013.10.001

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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
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
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
  • Health Sciences › Medicine › Epidemiology › 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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