Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death.

TitleInsulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death.
Publication TypeJournal Article
Year of Publication2019
AuthorsShi, C, Booth, LN, Murphy, CT
JournalElife
Volume8
Date Published2019 Jul 08
ISSN2050-084X
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.

DOI10.7554/eLife.46413
Alternate JournalElife
PubMed ID31282862
Grant ListPioneer 1DP1OD020400-01 / / NIH Office of the Director /
NA / / Glenn Foundation for Medical Research /