Reference - Detail
| RRC ID | 87988 |
|---|---|
| Author | Bahr L, Amrit FRG, Silvia PE, Wayhs B, Osman GA, Devare MN, Henry H, Bui D, Choe M, Naim N, Champion M, Man Y, Olsen CP, Ghazi A. |
| Title | LIPL-1 and LIPL-2 are TCER-1-regulated lysosomal lipases with distinct roles in immunity and fertility. |
| Journal | PLoS Genet |
| Abstract |
Reproduction and immunity are energy intensive processes that often compete for resources, leading to trade-offs across species. Lipid metabolism integrates these processes, particularly during stressful conditions such as pathogenic infections, yet the underlying molecular mechanisms remain poorly understood. TCER-1, the C. elegans homolog of mammalian TCERG1, suppresses immunity and promotes fertility, especially upon maternal infection. Here, we show that TCER-1 coordinates this balance by regulating two conserved lysosomal lipases, lipl-1 and lipl-2. Using transcriptomic, lipidomic, and molecular-genetic analyses, we demonstrate that both lipases mediate infection-induced lipid remodeling but with distinct outcomes: lipl-1 promotes immunity, whereas, lipl-2 does not. LIPL-1 catalyzes the accumulation of specific ceramide species, including Cer 17:1;O2/24:0, whose supplementation rescues the immunity phenotypes of tcer-1;lipl-1 mutants and enhances post-infection survival of wild-type animals. Both lipases influence fertility with lipl-2 playing a key role in maintaining embryonic-eggshell integrity during maternal infection and aging. Remarkably, expression of human lysosomal acid lipase (hLAL/LIPA), the ortholog of 'lipl' genes, restores immunity defects triggered by lipl-1 loss and enhances immune resilience but does not significantly ameliorate the fertility defects. Together, these findings reveal distinct roles for lipl-1 and lipl-2 in modulating lipid species that link immune defense, reproductive fitness and healthspan through a potentially conserved mechanism. |
| Volume | 21(12) |
| Pages | e1011804 |
| Published | 2025-12-1 |
| DOI | 10.1371/journal.pgen.1011804 |
| PII | PGENETICS-D-25-00799 |
| PMID | 41385585 |
| PMC | PMC12716718 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Fertility* / genetics Lipase* / genetics Lipase* / metabolism Lipid Metabolism / genetics Lysosomes / enzymology |
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| The most frequently cited source | Blogs |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| C.elegans | tm1452 |