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ATG-9-Mediated Synaptic Autophagy Promotes Aversive Learning under Stress in C. elegans

ABSTRACT: Autophagy is a degradative process that maintains cellular homeostasis and functions. Autophagy biogenesis at neuronal synapses requires synaptic proteins, but its impact on synaptic functions is incompletely understood. Here we show that, in Caenorhabditis elegans, synaptic ATG-9, the only transmembrane protein in the autophagy pathway, contributes to aversive learning under mitochondrial stress. Analysis of the neuronal translatome reveals that autophagy is upregulated by stress in the octopaminergic RIC neuron and it promotes aversive learning. Inactivating autophagy genes in RIC, including atg-9, reduces aversive learning. Mitochondrial stress increases synaptic ATG-9 abundance through AP-1- and AP-2-dependent exocytosis and endocytosis, respectively, and blocking synaptic ATG-9 trafficking impairs aversive learning. Synaptic ATG-9 levels are independent of key autophagy genes, such as bec-1/Beclin1 and lgg-1/GABARAP, suggesting that mechanisms other than canonical autophagy regulate synaptic ATG-9 in aversive learning. Our work underscores the importance of synaptic autophagy in stress-induced behavioral adaptations and reveals molecular details of aversive learning at single-neuron level.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE300122 | GEO | 2026/05/21

REPOSITORIES: GEO

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