Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans, 2024, Cornell+

Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans
Cornell, Rebecca; Cao, Wei; Harradine, Bernie; Godini, Rasoul; Handley, Ava; Pocock, Roger

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 UPR mt in physiological conditions is not well understood. Here, we show that gamma-aminobutyric acid (GABA) inhibits, and acetylcholine (ACh) promotes the UPR mt in the Caenorhabditis elegans intestine. GABA controls the UPR mt by regulating extrasynaptic ACh release through metabotropic GABA B receptors GBB-1/2. We find that elevated ACh levels in animals that are GABA-deficient or lack ACh degradative enzymes induce the UPR mt 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.

Link | PDF (Nature Communications) [Open Access]

 

In worms, though however —

---

 

It might still be relevant.

I still think there is a small possibility that EACh signalling is central to ME/CFS. The Wust pictures may show something odd going on with acetylcholinesterase.