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Translation suppression promotes stress granule formation and cell survival in response to cold shock

Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initia...

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Autores principales: Hofmann, Sarah, Cherkasova, Valeria, Bankhead, Peter, Bukau, Bernd, Stoecklin, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459856/
https://www.ncbi.nlm.nih.gov/pubmed/22875991
http://dx.doi.org/10.1091/mbc.E12-04-0296
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author Hofmann, Sarah
Cherkasova, Valeria
Bankhead, Peter
Bukau, Bernd
Stoecklin, Georg
author_facet Hofmann, Sarah
Cherkasova, Valeria
Bankhead, Peter
Bukau, Bernd
Stoecklin, Georg
author_sort Hofmann, Sarah
collection PubMed
description Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2α (eIF2α) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock–induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2α phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia.
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spelling pubmed-34598562012-12-16 Translation suppression promotes stress granule formation and cell survival in response to cold shock Hofmann, Sarah Cherkasova, Valeria Bankhead, Peter Bukau, Bernd Stoecklin, Georg Mol Biol Cell Articles Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2α (eIF2α) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock–induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2α phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia. The American Society for Cell Biology 2012-10-01 /pmc/articles/PMC3459856/ /pubmed/22875991 http://dx.doi.org/10.1091/mbc.E12-04-0296 Text en © 2012 Hofmann et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Hofmann, Sarah
Cherkasova, Valeria
Bankhead, Peter
Bukau, Bernd
Stoecklin, Georg
Translation suppression promotes stress granule formation and cell survival in response to cold shock
title Translation suppression promotes stress granule formation and cell survival in response to cold shock
title_full Translation suppression promotes stress granule formation and cell survival in response to cold shock
title_fullStr Translation suppression promotes stress granule formation and cell survival in response to cold shock
title_full_unstemmed Translation suppression promotes stress granule formation and cell survival in response to cold shock
title_short Translation suppression promotes stress granule formation and cell survival in response to cold shock
title_sort translation suppression promotes stress granule formation and cell survival in response to cold shock
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459856/
https://www.ncbi.nlm.nih.gov/pubmed/22875991
http://dx.doi.org/10.1091/mbc.E12-04-0296
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