@article{1f27d7d46eef44cc911432fee25fc7e1,
title = "A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage",
abstract = "Somatic cells age and die, but the germ-cell lineage is immortal. In Caenorhabditis elegans, germline immortality involves proteostasis renewal at the beginning of each new generation, when oocyte maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen. Oocyte maturation signals are known to trigger protein-aggregate removal via lysosome acidification. Our findings suggest that lysosomes are acidified as a consequence of changes in endoplasmic reticulum activity that permit assembly of the lysosomal V-ATPase, which in turn allows lysosomes to clear the aggregates via microautophagy. We define two functions for mitochondria, both of which appear to be independent of ATP generation. Many genes from the screen also regulate lysosome acidification and age-dependent protein aggregation in the soma, suggesting a fundamental mechanistic link between proteostasis renewal in the germline and somatic longevity.",
author = "Madhuja Samaddar and J{\'e}r{\^o}me Goudeau and Melissa Sanchez and Hall, {David H.} and Bohnert, {K. Adam} and Maria Ingaramo and Cynthia Kenyon",
note = "Funding Information: We thank colleagues in the Kenyon lab and at Calico Life Sciences for advice and discussion, and Daniel Gottschling and Calvin Jan for comments on the manuscript. Special thanks to Andrew Dillin (University of California, Berkeley) for sharing his transmission electron microscopy resources, and Peichuan Zhang for help with converting the RNAi collection format. We thank Robert Keyser for help with liquid handling robotics for the primary screen, and Kayley Hake for suggesting skewness as a way to capture puncta/aggregate formation in microscopy images. Peichuan Zhang and Rex Kerr helped to analyze somatic KIN-19::split-wrmScarlet aggregation. We thank Di Chen for sharing the DCL565 and DCL569 strains. Some C. elegans strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). The endogenously tagged V-ATPase and MosSCI C. elegans strains were generated by SunyBiotech, China. Some illustrations in Figures 1 and 7 were created with BioRender.com. The study was supported by Calico Life Sciences, DHH was supported by NIH OD010943, and MeS was supported by HHMI funding to A Dillin. Funding Information: We thank colleagues in the Kenyon lab and at Calico Life Sciences for advice and discussion, and Daniel Gottschling and Calvin Jan for comments on the manuscript. Special thanks to Andrew Dillin (University of California, Berkeley) for sharing his transmission electron microscopy resources, and Peichuan Zhang for help with converting the RNAi collection format. We thank Robert Keyser for help with liquid handling robotics for the primary screen, and Kayley Hake for suggesting skewness as a way to capture puncta/aggregate formation in microscopy images. Peichuan Zhang and Rex Kerr helped to analyze somatic KIN-19::split-wrmScarlet aggregation. We thank Di Chen for sharing the DCL565 and DCL569 strains. Some C. elegans strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). The endogenously tagged V-ATPase and MosSCI C. elegans strains were generated by SunyBiotech, China. Some illustrations in Figures 1 and 7 were created with BioRender.com. The study was supported by Calico Life Sciences, DHH was supported by NIH OD010943, and MeS was supported by HHMI funding to A Dillin.Funder Grant reference number Author Calico Life Sciences LLC Madhuja Samaddar J?r?me Goudeau K Adam Bohnert Maria Ingaramo Cynthia Kenyon National Institutes of Health OD010943 David H Hall Howard Hughes Medical Institute Melissa Sanchez The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Samaddar et al.",
year = "2021",
doi = "10.7554/ELIFE.62653",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}