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

Morita, M. et al. (2013) mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metabolism, 18(5), pp. 698-711. (doi: 10.1016/j.cmet.2013.10.001)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Zheng, Mr Liang and Gottlieb, Professor Eyal
• Authors: Morita, M., Gravel, S., 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., and Sonenberg, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Metabolism
• ISSN: 1550-4131
• ISSN (Online): 1932-7420