Reference - Detail
| RRC ID | 88141 |
|---|---|
| Author | Zhai Y, Wang T, Han J, Wu M, Gong M, Li W, Zhang Z. |
| Title | Lysosomal control of proteostasis and reproductive capacity by conserved LMD-3 protein in C. elegans. |
| Journal | Sci Adv |
| Abstract |
Human female fertility declines markedly with age, a pattern mirrored in C. elegans fecundity. This shared vulnerability stems from evolutionarily conserved molecular pathways. A growing body of evidence links impaired proteostasis-the cell's ability to manage its proteins-to this age-related fertility drop in both species, although the underlying mechanisms are not fully understood. Here, we identify that LMD-3, a LysM domain protein, is a critical regulator of proteostasis and reproductive capacity in C. elegans. Deficiency of lmd-3 leads to notable defects in oxidation resistance and constitutively high cellular stress responses. We demonstrate that LMD-3, localized to the lysosome, interacts with vitellogenin and a proton-pumping V-type ATPase via its TLDc domain to regulate lysosomal function and maintain yolk protein homeostasis. We also found that supplementing with vitamin B12 can restore fertility in lmd-3 mutants by reducing oxidative stress and improving lysosomal function. These findings establish a model for studying reproductive health and finding potential therapeutic strategies. |
| Volume | 11(48) |
| Pages | eadz3192 |
| Published | 2025-11-28 |
| DOI | 10.1126/sciadv.adz3192 |
| PMID | 41296857 |
| PMC | PMC12652258 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / chemistry Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Female Fertility Lysosomes* / metabolism Mutation Oxidative Stress Proteostasis* Reproduction Vacuolar Proton-Translocating ATPases / metabolism Vitellogenins / metabolism |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.5 |
| Resource | |
| C.elegans | tm2345 |