IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50973-y.html
   My bibliography  Save this article

Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans

Author

Listed:
  • Rebecca Cornell

    (Monash University)

  • Wei Cao

    (Monash University)

  • Bernie Harradine

    (Monash University)

  • Rasoul Godini

    (Monash University)

  • Ava Handley

    (Monash University)

  • Roger Pocock

    (Monash University)

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.

Suggested Citation

  • Rebecca Cornell & Wei Cao & Bernie Harradine & Rasoul Godini & Ava Handley & Roger Pocock, 2024. "Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50973-y
    DOI: 10.1038/s41467-024-50973-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50973-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50973-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ji Ying Sze & Martin Victor & Curtis Loer & Yang Shi & Gary Ruvkun, 2000. "Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant," Nature, Nature, vol. 403(6769), pages 560-564, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ria S. Peesapati & Brianna L. Austin-Byler & Fathima Zahra Nawaz & Jonathan B. Stevenson & Stanelle A. Mais & Rabia N. Kaya & Michael G. Hassan & Nabraj Khanal & Alexandra C. Wells & Deena Ghiai & Ani, 2024. "A specific folate activates serotonergic neurons to control C. elegans behavior," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Hillary A. Miller & Shijiao Huang & Elizabeth S. Dean & Megan L. Schaller & Angela M. Tuckowski & Allyson S. Munneke & Safa Beydoun & Scott D. Pletcher & Scott F. Leiser, 2022. "Serotonin and dopamine modulate aging in response to food odor and availability," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Mikaeli Anne Carmichael & Rebecca Louise Thomson & Lisa Jane Moran & Thomas Philip Wycherley, 2021. "The Impact of Menstrual Cycle Phase on Athletes’ Performance: A Narrative Review," IJERPH, MDPI, vol. 18(4), pages 1-24, February.
    4. Tripti Nair & Brandy A. Weathers & Nicole L. Stuhr & James D. Nhan & Sean P. Curran, 2024. "Serotonin deficiency from constitutive SKN-1 activation drives pathogen apathy," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50973-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.