A Genome Scale Screen for Mutants with Delayed Exit from Mitosis: Ire1-Independent Induction of Autophagy Integrates ER Homeostasis into Mitotic Lifespan

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High throughput studies have yielded large collections of genes that together govern post-mitotic longevity in eukaryotic cells. However, it is also clear that mitotic lifespan is subject to regulation via intricate mechanisms that facilitate exit from mitosis. Elucidating these mechanisms has been the subject of intensive research in part because failure to exit mitosis is associated with cell immortalization, a hallmark of neoplastic growth. Yet, to date mechanisms driving mitotic lifespan remain poorly characterized largely due to the absence of a feasible high throughput screening platform. Here we describe a large-scale screen in yeast Saccharomyces cerevisiae for mutants that undergo an atypically high number of cell divisions before exiting mitosis. We report an intricate cross talk between Endoplasmic Reticulum (ER) homeostasis and mitotic longevity. Autophagy, activated in response to ER stress, delays mitotic senescence in part by removing high molecular weight cytoplasmic protein aggregates. This evolutionarily conserved catabolic network similarly extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data highlight that, similar to its role in extending post-mitotic lifespan, catabolism of protein aggregates is among the drivers of mitotic longevity in eukaryotes.

Vyšlo v časopise: A Genome Scale Screen for Mutants with Delayed Exit from Mitosis: Ire1-Independent Induction of Autophagy Integrates ER Homeostasis into Mitotic Lifespan. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005429
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005429

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