Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
- Princeton University, United States
- Stanford University, United States
Abstract
C. elegans lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator. Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death. In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulated Zn-finger transcription factor PQM-1 promote seminal-fluid-induced killing. Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induced death until self-sperm are exhausted, increasing the chances that mothers will survive through reproduction. Mothers combat males' hijacking of their IIS pathway by expressing an insulin antagonist that keeps her healthy through the activity of pro-longevity factors, as long as she has her own sperm to utilize.
Data availability
Microarray data are available at the following links:"L4 fog-2(q71) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7332"L4 fem-3(q20) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7333"D3 mated fog-2(q71) vs pqm-1(ok485) hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7334
Article and author information
Author details
Funding
NIH Office of the Director (Pioneer 1DP1OD020400-01)
- Coleen T Murphy
Glenn Foundation for Medical Research (NA)
- Coleen T Murphy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Matt Kaeberlein, University of Washington, United States
Version history
- Received: February 27, 2019
- Accepted: July 7, 2019
- Accepted Manuscript published: July 8, 2019 (version 1)
- Version of Record published: August 16, 2019 (version 2)
Copyright
© 2019, Shi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
eLife 8:e46413.
https://doi.org/10.7554/eLife.46413
Further reading
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- Evolutionary Biology
- Genetics and Genomics
Young Caenorhabditis elegans hermaphrodites use their own sperm to protect against the negative consequences of mating.
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- Genetics and Genomics
Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker’s yeast Saccharomyces cerevisiae, the X- and Y’-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y’-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y’-elements) in telomere maintenance. Deletion of Y’-elements (SY12YΔ), X-elements (SY12XYΔ+Y), or both X- and Y’-elements (SY12XYΔ) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12YΔ, SY12XYΔ+Y, and SY12XYΔ cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X- and Y’-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.
