RRC ID 45564
Author Ghavidel A, Baxi K, Ignatchenko V, Prusinkiewicz M, Arnason TG, Kislinger T, Carvalho CE, Harkness TA.
Title A Genome Scale Screen for Mutants with Delayed Exit from Mitosis: Ire1-Independent Induction of Autophagy Integrates ER Homeostasis into Mitotic Lifespan.
Journal PLoS Genet
Abstract Proliferating eukaryotic cells undergo a finite number of cell divisions before irreversibly exiting mitosis. Yet pathways that normally limit the number of cell divisions remain poorly characterized. Here we describe a screen of a collection of 3762 single gene mutants in the yeast Saccharomyces cerevisiae, accounting for 2/3 of annotated yeast ORFs, to search for mutants that undergo an atypically high number of cell divisions. Many of the potential longevity genes map to cellular processes not previously implicated in mitotic senescence, suggesting that regulatory mechanisms governing mitotic exit may be broader than currently anticipated. We focused on an ER-Golgi gene cluster isolated in this screen to determine how these ubiquitous organelles integrate into mitotic longevity. We report that a chronic increase in ER protein load signals an expansion in the assembly of autophagosomes in an Ire1-independent manner, accelerates trafficking of high molecular weight protein aggregates from the cytoplasm to the vacuoles, and leads to a profound enhancement of daughter cell production. We demonstrate that this catabolic network is evolutionarily conserved, as it also extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data provide evidence that catabolism of protein aggregates, a natural byproduct of high protein synthesis and turn over in dividing cells, is among the drivers of mitotic longevity in eukaryotes.
Volume 11(8)
Pages e1005429
Published 2015-8-1
DOI 10.1371/journal.pgen.1005429
PMID 26247883
PMC PMC4527830
MeSH Animals Autophagy* Caenorhabditis elegans Caenorhabditis elegans Proteins / physiology* Endoplasmic Reticulum / metabolism Endoplasmic Reticulum Stress Genome, Fungal Genome, Helminth Homeostasis Membrane Glycoproteins / physiology* Mitosis* Protein Aggregates Protein-Serine-Threonine Kinases / physiology* Reproduction Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / physiology* Unfolded Protein Response Vesicular Transport Proteins / genetics
IF 5.175
Times Cited 15
C.elegans tm5219