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A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage.

Authors
  • Bohnert, K Adam1, 2
  • Kenyon, Cynthia1, 2
  • 1 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
  • 2 Calico Life Sciences, South San Francisco, California 94080, USA.
Type
Published Article
Journal
Nature
Publisher
Springer Nature
Publication Date
Nov 30, 2017
Volume
551
Issue
7682
Pages
629–633
Identifiers
DOI: 10.1038/nature24620
PMID: 29168500
Source
Medline
License
Unknown

Abstract

Although individuals age and die with time, an animal species can continue indefinitely, because of its immortal germ-cell lineage. How the germline avoids transmitting damage from one generation to the next remains a fundamental question in biology. Here we identify a lysosomal switch that enhances germline proteostasis before fertilization. We find that Caenorhabditis elegans oocytes whose maturation is arrested by the absence of sperm exhibit hallmarks of proteostasis collapse, including protein aggregation. Remarkably, sperm-secreted hormones re-establish oocyte proteostasis once fertilization becomes imminent. Key to this restoration is activation of the vacuolar H+-ATPase (V-ATPase), a proton pump that acidifies lysosomes. Sperm stimulate V-ATPase activity in oocytes by signalling the degradation of GLD-1, a translational repressor that blocks V-ATPase synthesis. Activated lysosomes, in turn, promote a metabolic shift that mobilizes protein aggregates for degradation, and reset proteostasis by enveloping and clearing the aggregates. Lysosome acidification also occurs during Xenopus oocyte maturation; thus, a lysosomal switch that enhances oocyte proteostasis in anticipation of fertilization may be conserved in other species.

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