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Proteasome activity contributes to pro-survival response upon mild mitochondrial stress in Caenorhabditis elegans

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dc.abstract.enDefects in mitochondrial function activate compensatory responses in the cell. Mitochondrial stress that is caused by unfolded proteins inside the organelle induces a transcriptional response (termed the “mitochondrial unfolded protein response” [UPRmt]) that is mediated by activating transcription factor associated with stress 1 (ATFS-1). The UPRmt increases mitochondrial protein quality control. Mitochondrial dysfunction frequently causes defects in the import of proteins, resulting in the accumulation of mitochondrial proteins outside the organelle. In yeast, cells respond to mistargeted mitochondrial proteins by increasing activity of the proteasome in the cytosol (termed the “unfolded protein response activated by mistargeting of proteins” [UPRam]). The presence and relevance of this response in higher eukaryotes is unclear. Here, we demonstrate that defects in mitochondrial protein import in Caenorhabditis elegans lead to proteasome activation and life span extension. Both proteasome activation and life span prolongation partially depend on ATFS-1, despite its lack of influence on proteasomal gene transcription. Importantly, life span prolongation depends on the fully assembled proteasome. Our data provide a link between mitochondrial dysfunction and proteasomal activity and demonstrate its direct relevance to mechanisms that promote longevity.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorChacinska, Agnieszka
dc.contributor.authorSladowska, Maria
dc.contributor.authorKim, Min-Ji
dc.contributor.authorMussulini, Ben Hur Marins
dc.contributor.authorMohanraj, Karthik
dc.contributor.authorTopf, Ulrike
dc.contributor.authorDrabikowski, Krzysztof
dc.contributor.authorTurek, Michał
dc.contributor.authorSerwa, Remigiusz
dc.date.accessioned2024-01-25T18:20:43Z
dc.date.available2024-01-25T18:20:43Z
dc.date.copyright2021-07-12
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number7
dc.description.versionFINAL_PUBLISHED
dc.description.volume19
dc.identifier.doi10.1371/JOURNAL.PBIO.3001302
dc.identifier.issn1544-9173
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/117291
dc.identifier.weblinkhttps://dx.plos.org/10.1371/journal.pbio.3001302
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofPLoS Biology
dc.relation.pagese3001302 (1-32)
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.plbrak
dc.titleProteasome activity contributes to pro-survival response upon mild mitochondrial stress in Caenorhabditis elegans
dc.typeJournalArticle
dspace.entity.typePublication