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Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress.

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cris.lastimport.scopus2024-02-12T20:37:02Z
dc.abstract.enPrevious studies demonstrated that cells inhibit protein synthesis as a compensatory mechanism for mitochondrial dysfunction. Protein synthesis can be attenuated by 1) the inhibition of mTOR kinase, which results in a decrease in the phosphorylation of S6K1 and 4E-BP1 proteins, and 2) an increase in the phosphorylation of eIF2α protein. The present study investigated both of these pathways under conditions of short-term acute and long-term mitochondrial stress. Short-term responses were triggered in mammalian cells by treatment with menadione, antimycin A, or CCCP. Long-term mitochondrial stress was induced by prolonged treatment with menadione or rotenone and expression of genetic alterations, such as knocking down the MIA40 oxidoreductase or knocking out NDUFA11 protein. Short-term menadione, antimycin A, or CCCP cell treatment led to the inhibition of protein synthesis, accompanied by a decrease in mTOR kinase activity, an increase in the phosphorylation of eIF2α (Ser51), and an increase in the level of ATF4 transcription factor. Conversely, long-term stress led to a decrease in eIF2α (Ser51) phosphorylation and ATF4 expression and to an increase in S6K1 (Thr389) phosphorylation. Thus, under long-term mitochondrial stress, cells trigger long-lasting adaptive responses for protection against excessive inhibition of protein synthesis.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorUrbańska, Małgorzata
dc.contributor.authorJAWORSKI, JACEK
dc.contributor.authorSamluk, Łukasz
dc.contributor.authorKisielewska, Katarzyna
dc.contributor.authorMohanraj, Karthik
dc.contributor.authorMachnicka, Katarzyna
dc.contributor.authorLiszewska, Ewa
dc.contributor.authorChacińska, Agnieszka
dc.contributor.authorKim, Minji
dc.date.accessioned2024-01-24T21:15:30Z
dc.date.available2024-01-24T21:15:30Z
dc.date.copyright2019-07-15
dc.date.issued2019
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number15
dc.description.versionFINAL_PUBLISHED
dc.description.volume30
dc.identifier.doi10.1091/MBC.E18-10-0628
dc.identifier.issn1059-1524
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/104099
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofMolecular Biology of the Cell
dc.relation.pages1864-1877
dc.rightsCC-BY-NC-SA
dc.sciencecloudnosend
dc.titleCytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress.
dc.typeJournalArticle
dspace.entity.typePublication