caa a22 4500 528785370 20190908091347.0 cr unu---uuuuu 180924e201511 xx s 000 0 eng 10.3929/ethz-b-000107259 doi 10.7554/eLife.06197 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/107259 Saarikangas Juha Protein aggregates are associated with replicative aging without compromising protein quality control [Elektronische Daten] [Juha Saarikangas, Yves Barral] Open access ethresearch Differentiation of cellular lineages is facilitated by asymmetric segregation of fate determinants between dividing cells. In budding yeast, various aging factors segregate to the aging (mother)-lineage, with poorly understood consequences. In this study, we show that yeast mother cells form a protein aggregate during early replicative aging that is maintained as a single, asymmetrically inherited deposit over the remaining lifespan. Surprisingly, deposit formation was not associated with stress or general decline in proteostasis. Rather, the deposit-containing cells displayed enhanced degradation of cytosolic proteasome substrates and unimpaired clearance of stress-induced protein aggregates. Deposit formation was dependent on Hsp42, which collected non-random client proteins of the Hsp104/Hsp70-refolding machinery, including the prion Sup35. Importantly, loss of Hsp42 resulted in symmetric inheritance of its constituents and prolonged the lifespan of the mother cell. Together, these data suggest that protein aggregation is an early aging-associated differentiation event in yeast, having a two-faceted role in organismal fitness. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Barral Yves joint author eLife Cambridge : eLife Sciences Publications 4, p. e06197 2050-084X http://hdl.handle.net/20.500.11850/107259 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/107259 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 100 1- Saarikangas Juha ETHRESEARCH 700 1- Barral Yves joint author ETHRESEARCH 773 0- eLife Cambridge : eLife Sciences Publications 4, p. e06197 2050-084X BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access