Mitochondrial energy state controls AMPK-mediated foraging behavior in C. elegans

Area of Science:

• Cellular biology
• Neuroscience
• Behavioral biology

Background:

• Metabolic cues regulate organismal behavior based on food availability.
• Mitochondria are central metabolic hubs, with protonmotive force (PMF) integrating mitochondrial status.
• The role of PMF in metabolic signaling and behavior is not well understood.

Purpose of the Study:

• To investigate the role of mitochondrial PMF in governing metabolic signaling and food-related behaviors.
• To determine if PMF dissipation in specific tissues can trigger behavioral responses to food deprivation.

Main Methods:

• Utilized optogenetics to manipulate PMF in *Caenorhabditis elegans* tissues.
• Assessed locomotor responses to acute food deprivation.
• Investigated the involvement of AMP-activated protein kinase (AMPK) in neurons and intestine.
• Examined the role of mitochondrial dynamics and axonal trafficking.

Main Results:

• PMF reduction specifically in the intestine initiated locomotor responses to food deprivation.
• This behavioral adaptation required neuronal AMPK, not intestinal AMPK.
• The process involved mitochondrial dynamics and axonal trafficking.

Conclusions:

• Intestinal PMF acts as a critical internal metabolic cue signaling food availability.
• A bottom-up signaling pathway exists where intestinal PMF changes activate neuronal AMPK.
• This pathway promotes foraging behavior in response to metabolic cues.