A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage

eLife

Maria Ingaramo¹  Cynthia Kenyon¹  Jérôme Goudeau¹  Madhuja Samaddar¹  K Adam Bohnert¹  Melissa Sanchez²  David H Hall³ 

[1] Calico Life Sciences LLC, South San Francisco, United States;Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, United States;Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States;

关键词: proteostasis;    germ lineage;    oocyte maturation;    genetic screen;    lysosome acidification;    C. elegans;   

DOI  :  10.7554/eLife.62653

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY