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Cell Metab. 2013 Nov 5;18(5):698-711. doi: 10.1016/j.cmet.2013.10.001.

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

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1
Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.

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.

PMID:
24206664
DOI:
10.1016/j.cmet.2013.10.001
[Indexed for MEDLINE]
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