LIN-24 as a Molecular Switch: Dual Cytotoxic and Cytoprotective Roles of an Aerolysin-Like Protein in C. elegans

Sharoen Lim, Yu Ming (2025) LIN-24 as a Molecular Switch: Dual Cytotoxic and Cytoprotective Roles of an Aerolysin-Like Protein in C. elegans. Journal of Applied Toxicology. pp. 1-7. ISSN 1099-1263

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Abstract

LIN-24, an aerolysin-like pore-forming protein in Caenorhabditis elegans, exemplifies how ancient cytolytic mechanisms have evolved into regulated cellular processes. Initially identified for inducing nonapoptotic, engulfment-dependent cell death in vulval precursor cells, LIN-24 has emerged as a multifunctional regulator of metabolism, stress resilience, and immune defense. Its expression increases during starvation and bacterial infection, promoting lipid mobilization, mitochondrial remodeling, and activation of DAF-16, MAPK, and SKN-1 pathways, thereby enhancing survival and pathogen resistance. Conversely, gain-of-function mutations trigger cytotoxic membrane disruption, illustrating LIN-24's dual role in cytotoxicity and cytoprotection. Despite these advances, its precise structure, regulatory mechanisms, and interaction networks remain undefined. Understanding how LIN-24's pore-forming activity is contextually controlled will clarify how eukaryotes repurpose toxic domains for adaptive functions and may provide translational insights into human pore-forming proteins such as perforins and gasdermins involved in immune defense and programmed cell death.

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