NEURONAL AUTOPHAGY AS A REGULATOR OF FEEDING BEHAVIOR: THE ROLE OF <EM>EGLI-1 </EM>IN <EM>C. ELEGANS</EM>

Sensing and responding to food is essential for animal survival, and many of the underlying regulatory mechanisms are evolutionarily conserved. Dissecting the cellular and neuronal processes that control feeding behavior is therefore crucial for understanding metabolic disorders. However, the complexity of mammalian systems poses major experimental challenges. The nematode Caenorhabditis elegans offers a powerful alternative, combining a fully mapped nervous system with diverse, quantifiable food-related behaviors.
We previously identified the C. elegans gene egli-1 as a key regulator of food-dependent behavioral adaptation. Loss-of-function mutants fail to adjust to food deprivation and instead behave as if persistently well-fed. Notably, the mammalian orthologue of egli-1, TMEM41B, has been implicated in autophagy, a conserved intracellular nutrient-sensing pathway.
Here, we provide in vivo evidence that egli-1 regulates autophagy in C. elegans, using fluorescent reporters and western blot analyses that reveal aberrant autophagic responses in egli-1 mutants. Behavioral analyses further demonstrate that neuronal-specific knockdown of egli-1 disrupts multiple food-related behaviors, including, food chemotaxis (reduced ability to navigate towards food sources); enhanced slowing response (inability to modulate locomotion speed upon food encounter) and egg-laying regulation (disrupted reproductive strategies in response to nutritional status). Importantly, targeted activation of neuronal autophagy restores wild-type behavioral responses.
These findings support a model in which neuronal autophagy acts as a molecular switch enabling behavioral flexibility in response to nutritional state. By defining the subcellular mechanisms linking autophagy to sensorimotor integration, this work highlights conserved pathways with potential relevance to human metabolic disorders.