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

• Verfasst von: Hofmann, Sarah [VerfasserIn]
• Verfasst von: Khaimov, Valeria [VerfasserIn]
• Verfasst von: Bankhead, Peter [VerfasserIn]
• Verfasst von: Bukau, Bernd [VerfasserIn]
• Verfasst von: Stoecklin, Georg [VerfasserIn]
• Titel: Translation suppression promotes stress granule formation and cell survival in response to cold shock
• Verf.angabe: Sarah Hofmann, Valeria Cherkasova, Peter Bankhead, Bernd Bukau, and Georg Stoecklin ; Monitoring Editor: Sandra Wolin, Yale University
• E-Jahr: 2012
• Jahr: 8 Aug 2012
• Umfang: 15 S.
• Fussnoten: Gesehen am 16.08.2018
• Titel Quelle: Enthalten in: Molecular biology of the cell
• Ort Quelle: Bethesda, Md. : American Society for Cell Biology, 1992
• Jahr Quelle: 2012
• Band/Heft Quelle: 23(2012), 19, Seite 3786-3800
• ISSN Quelle: 1939-4586
• DOI: doi:10.1091/mbc.e12-04-0296
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580108490

Abstract

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.