@article{3af467d5ce8545c1ad3b50e3755e9a8a,
title = "MTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation",
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.",
author = "Masahiro Morita and Gravel, {Simon Pierre} and Val{\'e}rie Ch{\'e}nard and Kristina Sikstr{\"o}m and Liang Zheng and Tommy Alain and Valentina Gandin and Daina Avizonis and Meztli Arguello and Chadi Zakaria and Shannon McLaughlan and Yann Nouet and Arnim Pause and Michael Pollak and Eyal Gottlieb and Ola Larsson and Julie St-Pierre and Ivan Topisirovic and Nahum Sonenberg",
note = "Funding Information: We thank Y. Liu for providing PP242 and Ink1341, M.C. Gingras for technical assistance with metabolic cages, V. Henderson for editing the manuscript, and C. Lister, P. Kirk, A. Sylvestre, S. Perreault, and I. Harvey for assistance. Research was supported by a Terry Fox Research Institute team grant (TFF-116128) to N.S., I.T., M.P., D.A., A.P., and J.S-P. and grants from the Canadian Institutes of Health Research (CIHR MOP-7214 to N.S.; MOP-115195 to I.T.; MOP-106603 to J.S-P.) and the Canadian Cancer Society Research Institute (CCSRI 16208 to N.S.). I.T. is a recipient of CIHR New Investigator Salary Award. J.S-P. is an FRSQ scholar. M.M. is a recipient of a CIHR-funded Chemical Biology Postdoctoral fellowship and Canadian Diabetes Association Postdoctoral fellowship. S.-P.G. is supported by a Canderel fellowship. Funding Information: Goodman Cancer Research Centre Metabolomics Core Facility is supported by the Canada Foundation of Innovation, The Dr. John R. and Clara M. Fraser Memorial Trust, the Terry Fox Foundation, the Canadian Institutes of Health Research, and McGill University. The Qu{\'e}bec/Eastern Canada High Field NMR Facility is supported by the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, the Qu{\'e}bec minist{\`e}re de la recherche en science et technologie, and McGill University. ",
year = "2013",
month = nov,
day = "5",
doi = "10.1016/j.cmet.2013.10.001",
language = "English (US)",
volume = "18",
pages = "698--711",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}