期刊
EMBO JOURNAL
卷 35, 期 10, 页码 1058-1076出版社
WILEY-BLACKWELL
DOI: 10.15252/embj.201593118
关键词
mTOR; mTORC1; lysosomes; stress; translation
资金
- Metabolomics Core Technology Platform of the Excellence cluster CellNetworks (University of Heidelberg)
- Deutsche Forschungsgemeinschaft [ZUK 40/2010-3009262]
- European Research Council under the European Union's Seventh Framework Programme via an ERC Starting Grant [260602]
- ERC Advanced Grant (Syngene)
- HPLC-based intracellular amino acid measurements
- European Research Council (ERC) [260602] Funding Source: European Research Council (ERC)
Amino acids regulate TOR complex 1 (TORC1) via two counteracting mechanisms, one activating and one inactivating. The presence of amino acids causes TORC1 recruitment to lysosomes where TORC1 is activated by binding Rheb. How the absence of amino acids inactivates TORC1 is less well understood. Amino acid starvation recruits the TSC1/TSC2 complex to the vicinity of TORC1 to inhibit Rheb; however, the upstream mechanisms regulating TSC2 are not known. We identify here the eIF4A-containing eIF4F translation initiation complex as an upstream regulator of TSC2 in response to amino acid withdrawal in Drosophila. We find that TORC1 and translation preinitiation complexes bind each other. Cells lacking eIF4F components retain elevated TORC1 activity upon amino acid removal. This effect is specific for eIF4F and not a general consequence of blocked translation. This study identifies specific components of the translation machinery as important mediators of TORC1 inactivation upon amino acid removal.
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