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

## TL;DR

The LIN-24 protein in C. elegans has both harmful and protective roles, showing how ancient toxic mechanisms evolved into regulated cellular functions.

## Contribution

LIN-24 is revealed as a dual-function protein with roles in cytotoxicity and cytoprotection, linking ancient cytolytic mechanisms to modern regulatory processes.

## Key findings

- LIN-24 regulates metabolism, stress resistance, and immunity by activating DAF-16, MAPK, and SKN-1 pathways.
- LIN-24's pore-forming activity is contextually controlled, balancing cytoprotection and cytotoxicity.
- LIN-24's function offers insights into the evolution of eukaryotic pore-forming proteins.

## 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.

LIN‐24 is an aerolysin‐like pore‐forming protein in
Caenorhabditis elegans
that illustrates how ancient cytolytic toxins are repurposed for adaptive cellular functions. Beyond inducing nonapoptotic cell death, LIN‐24 regulates metabolism, stress resistance, and immunity during starvation and infection by activating DAF‐16, MAPK, and SKN‐1 pathways. Its tightly controlled activity balances cytoprotection and cytotoxicity, offering insight into the evolution and regulation of eukaryotic pore‐forming proteins.