Publication Date:
2016-07-20
Description:
Publication date: 19 July 2016 Source: Cell Reports, Volume 16, Issue 3 Author(s): Sandra Malmgren Hill, Xinxin Hao, Johan Grönvall, Stephanie Spikings-Nordby, Per O. Widlund, Triana Amen, Anna Jörhov, Rebecca Josefson, Daniel Kaganovich, Beidong Liu, Thomas Nyström Age can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae , we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging—reduced endocytosis and protein aggregation—are interconnected and regulated by Vac17. Graphical abstract Teaser Cellular rejuvenation is enabled by asymmetrical inheritance of damaged proteins. Using a genome-wide imaging screen to identify asymmetry-generating genes, Hill et al. demonstrate a role for vesicle trafficking, membrane fusion, and the myosin-dependent adaptor protein Vac17 in the asymmetric inheritance of misfolded proteins and consequently in the regulation of lifespan.
Electronic ISSN:
2211-1247
Topics:
Biology
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