mTORC1 Controls Mitochondrial Activity and Biogenesis through 4E-BP-Dependent Translational Regulation

作者：Morita, Masahiro; Gravel, Simon-Pierre; Chenard, Valerie; Sikstrom, Kristina; Zheng, Liang; Alain, Tommy; Gandin, Valentina; Avizonis, Daina; Arguello, Meztli; Zakaria, Chadi; McLaughlan, Shannon; Nouet, Yann; Pause, Arnim; Pollak, Michael; Gottlieb, Eyal; Larsson, Ola; St-Pierre, Julie^*; Topisirovic, Ivan; Sonenberg, Nahum

来源：Cell Metabolism, 2013, 18(5): 698-711.

DOI：10.1016/j.cmet.2013.10.001

• MAMMALIAN TARGET
• DIFFERENTIAL TRANSLATION
• MOTIF PHOSPHORYLATION
• BINDING PARTNER
• CELL-GROWTH
• COMPLEX
• CANCER
• RAPTOR
• AKT
• ACTIVATION

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.

• 出版日期2013-11-5
• 单位河北医科大学