eIF 4A inactivates TORC 1 in response to amino acid starvation

Amino acids regulate TOR complex 1 ( TORC 1) via two counteracting mechanisms, one activating and one inactivating. The presence of amino acids causes TORC 1 recruitment to lysosomes where TORC 1 is activated by binding Rheb. How the absence of amino acids inactivates TORC 1 is less well understood. Amino acid starvation recruits the TSC 1/ TSC 2 complex to the vicinity of TORC 1 to inhibit Rheb; however, the upstream mechanisms regulating TSC 2 are not known. We identify here the eIF 4A‐containing eIF 4F translation initiation complex as an upstream regulator of TSC 2 in response to amino acid withdrawal in Drosophila . We find that TORC 1 and translation preinitiation complexes bind each other. Cells lacking eIF 4F components retain elevated TORC 1 activity upon amino acid removal. This effect is specific for eIF 4F and not a general consequence of blocked translation. This study identifies specific components of the translation machinery as important mediators of TORC 1 inactivation upon amino acid removal.