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TORC1-mediated sensing of chaperone activity alters glucose metabolism and extends lifespan.

dc.contributor.authorPerić, Matea
dc.contributor.authorLovrić, Anita
dc.contributor.authorŠarić, Ana
dc.contributor.authorMusa, Marina
dc.contributor.authorBou Dib, Peter
dc.contributor.authorRudan, Marina
dc.contributor.authorNikolić, Andrea
dc.contributor.authorSobočanec, Sandra
dc.contributor.authorMikecin, Ana-Matea
dc.contributor.authorDennerlein, Sven
dc.contributor.authorMilošević, Ira
dc.contributor.authorVlahoviček, Kristian
dc.contributor.authorRaimundo, Nuno
dc.contributor.authorKriško, Anita
dc.date.accessioned2018-01-05T12:48:56Z
dc.date.available2018-01-05T12:48:56Z
dc.date.issued2017
dc.relation.ISSN1474-9726
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/14988
dc.description.abstractProtein quality control mechanisms, required for normal cellular functioning, encompass multiple functions related to protein production and maintenance. However, the existence of communication between proteostasis and metabolic networks and its underlying mechanisms remain elusive. Here, we report that enhanced chaperone activity and consequent improved proteostasis are sensed by TORC1 via the activity of Hsp82. Chaperone enrichment decreases the level of Hsp82, which deactivates TORC1 and leads to activation of Snf1/AMPK, regardless of glucose availability. This mechanism culminates in the extension of yeast replicative lifespan (RLS) that is fully reliant on both TORC1 deactivation and Snf1/AMPK activation. Specifically, we identify oxygen consumption increase as the downstream effect of Snf1 activation responsible for the entire RLS extension. Our results set a novel paradigm for the role of proteostasis in aging: modulation of the misfolded protein level can affect cellular metabolic features as well as mitochondrial activity and consequently modify lifespan. The described mechanism is expected to open new avenues for research of aging and age-related diseases.
dc.languageeng
dc.language.isoeng
dc.relation315997
dc.relation316289
dc.relation337327
dc.rightsopenAccess
dc.rightsNamensnennung 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectageing; glucose starvation; mitochondria; protein chaperones; replicative lifespan; Snf1/AMPK; TORC1; yeast
dc.subject.ddc612
dc.titleTORC1-mediated sensing of chaperone activity alters glucose metabolism and extends lifespan.
dc.typejournalArticle
dc.identifier.doi10.1111/acel.12623
dc.type.versionpublishedVersion
dc.bibliographicCitation.volume16
dc.bibliographicCitation.issue5
dc.bibliographicCitation.firstPage994
dc.bibliographicCitation.lastPage1005
dc.type.subtypejournalArticle
dc.identifier.pmid28613034
dc.description.statuspeerReviewed
dc.bibliographicCitation.journalAging Cell


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