Peripheral peroxisomal β-oxidation engages neuronal serotonin signaling to drive stress-induced aversive memory in C. elegans.
Journal
Cell reports
Journal Volume
43
Journal Issue
4
Start Page
113996
ISSN
2211-1247
Date Issued
2024-04-23
Author(s)
Abstract
Physiological dysfunction confers negative valence to coincidental sensory cues to induce the formation of aversive associative memory. How peripheral tissue stress engages neuromodulatory mechanisms to form aversive memory is poorly understood. Here, we show that in the nematode C. elegans, mitochondrial disruption induces aversive memory through peroxisomal β-oxidation genes in non-neural tissues, including pmp-4/very-long-chain fatty acid transporter, dhs-28/3-hydroxylacyl-CoA dehydrogenase, and daf-22/3-ketoacyl-CoA thiolase. Upregulation of peroxisomal β-oxidation genes under mitochondrial stress requires the nuclear hormone receptor NHR-49. Importantly, the memory-promoting function of peroxisomal β-oxidation is independent of its canonical role in pheromone production. Peripheral signals derived from the peroxisomes target NSM, a critical neuron for memory formation under stress, to upregulate serotonin synthesis and remodel evoked responses to sensory cues. Our genetic, transcriptomic, and metabolomic approaches establish peroxisomal lipid signaling as a crucial mechanism that connects peripheral mitochondrial stress to central serotonin neuromodulation in aversive memory formation.
Subjects
C. elegans
CP: Cell biology
CP: Neuroscience
aversive memory
gut-brain signaling
mitochondria
neural activity
peroxisome
response properties
serotonin
stress
very-long-chain fatty acids
SDGs
Publisher
Cell Press
Type
journal article