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Title of Paper:Lysosomal control of proteostasis and reproductive capacity by conserved LMD-3 protein in C. elegans

Journal:Science Advances

Summary: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.

First Author:Yile Zhai,Tiantian Wang

Correspondence Author:Wenfei Li,张哲

All the Authors:Jiangxue Han,Mengxiao Wu,Meixi Gong

Translation or Not:No

Date of Publication:2025-11

Included Journals:SCI

Links to Published Journals:https://www.science.org/doi/10.1126/sciadv.adz3192

Release Time:2025-11-27