| RRC ID |
84046
|
| Author |
Cornell R, Cao W, Harradine B, Godini R, Handley A, Pocock R.
|
| Title |
Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans.
|
| Journal |
Nat Commun
|
| Abstract |
Neurons coordinate inter-tissue protein homeostasis to systemically manage cytotoxic stress. In response to neuronal mitochondrial stress, specific neuronal signals coordinate the systemic mitochondrial unfolded protein response (UPRmt) to promote organismal survival. Yet, whether chemical neurotransmitters are sufficient to control the UPRmt in physiological conditions is not well understood. Here, we show that gamma-aminobutyric acid (GABA) inhibits, and acetylcholine (ACh) promotes the UPRmt in the Caenorhabditis elegans intestine. GABA controls the UPRmt by regulating extra-synaptic ACh release through metabotropic GABAB receptors GBB-1/2. We find that elevated ACh levels in animals that are GABA-deficient or lack ACh-degradative enzymes induce the UPRmt through ACR-11, an intestinal nicotinic α7 receptor. This neuro-intestinal circuit is critical for non-autonomously regulating organismal survival of oxidative stress. These findings establish chemical neurotransmission as a crucial regulatory layer for nervous system control of systemic protein homeostasis and stress responses.
|
| Volume |
15(1)
|
| Pages |
6594
|
| Published |
2024-8-3
|
| DOI |
10.1038/s41467-024-50973-y
|
| PII |
10.1038/s41467-024-50973-y
|
| PMID |
39097618
|
| PMC |
PMC11297972
|
| MeSH |
Acetylcholine* / metabolism
Animals
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans* / physiology
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Intestines / physiology
Mitochondria* / metabolism
Neurons / metabolism
Oxidative Stress
Receptors, GABA-B / genetics
Receptors, GABA-B / metabolism
Signal Transduction*
Stress, Physiological
Synaptic Transmission / physiology
Unfolded Protein Response
alpha7 Nicotinic Acetylcholine Receptor / genetics
alpha7 Nicotinic Acetylcholine Receptor / metabolism
gamma-Aminobutyric Acid / metabolism
|
| Resource |
| C.elegans |
tm1406
tm1165 |
