eIF4A inactivates TORC1 in response to amino acid starvation

• Verfasst von: Tsokanos, Foivos Filippos [VerfasserIn]
• Verfasst von: Boutros, Michael [VerfasserIn]
• Titel: eIF4A inactivates TORC1 in response to amino acid starvation
• Verf.angabe: Foivos-Filippos Tsokanos, Marie-Astrid Albert, Constantinos Demetriades, Kerstin Spirohn, Michael Boutros and Aurelio A. Teleman
• E-Jahr: 2016
• Jahr: March 17, 2016
• Umfang: 19 S.
• Fussnoten: Gesehen am 20.05.2019
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationThe EMBO journal
• Ort Quelle: Heidelberg : EMBO Press, 1982
• Jahr Quelle: 2016
• Band/Heft Quelle: 35(2016), 10, Seite 1058-1076
• ISSN Quelle: 1460-2075
• DOI: doi:10.15252/embj.201593118
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: lysosomes
• Sach-SW: mTOR
• Sach-SW: mTORC1
• Sach-SW: stress
• Sach-SW: translation
• K10plus-PPN: 166594966X

Abstract

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.