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eIF4A inactivates TORC1 in response to amino acid starvation

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. Amin...

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Autores principales: Tsokanos, Foivos‐Filippos, Albert, Marie‐Astrid, Demetriades, Constantinos, Spirohn, Kerstin, Boutros, Michael, Teleman, Aurelio A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868951/
https://www.ncbi.nlm.nih.gov/pubmed/26988032
http://dx.doi.org/10.15252/embj.201593118
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author Tsokanos, Foivos‐Filippos
Albert, Marie‐Astrid
Demetriades, Constantinos
Spirohn, Kerstin
Boutros, Michael
Teleman, Aurelio A
author_facet Tsokanos, Foivos‐Filippos
Albert, Marie‐Astrid
Demetriades, Constantinos
Spirohn, Kerstin
Boutros, Michael
Teleman, Aurelio A
author_sort Tsokanos, Foivos‐Filippos
collection PubMed
description 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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spelling pubmed-48689512016-11-18 eIF4A inactivates TORC1 in response to amino acid starvation Tsokanos, Foivos‐Filippos Albert, Marie‐Astrid Demetriades, Constantinos Spirohn, Kerstin Boutros, Michael Teleman, Aurelio A EMBO J Articles 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. John Wiley and Sons Inc. 2016-03-17 2016-05-17 /pmc/articles/PMC4868951/ /pubmed/26988032 http://dx.doi.org/10.15252/embj.201593118 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Tsokanos, Foivos‐Filippos
Albert, Marie‐Astrid
Demetriades, Constantinos
Spirohn, Kerstin
Boutros, Michael
Teleman, Aurelio A
eIF4A inactivates TORC1 in response to amino acid starvation
title eIF4A inactivates TORC1 in response to amino acid starvation
title_full eIF4A inactivates TORC1 in response to amino acid starvation
title_fullStr eIF4A inactivates TORC1 in response to amino acid starvation
title_full_unstemmed eIF4A inactivates TORC1 in response to amino acid starvation
title_short eIF4A inactivates TORC1 in response to amino acid starvation
title_sort eif4a inactivates torc1 in response to amino acid starvation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868951/
https://www.ncbi.nlm.nih.gov/pubmed/26988032
http://dx.doi.org/10.15252/embj.201593118
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