Author
Listed:
- Sabnam Sahin Rahman
(Aruna Asaf Ali Marg)
- Shreya Bhattacharjee
(Aruna Asaf Ali Marg)
- Simran Motwani
(Aruna Asaf Ali Marg)
- Govind Prakash
(Aruna Asaf Ali Marg)
- Rajat Ujjainiya
(CSIR-Institute of Genomics and Integrative Biology
Academy of Scientific and Innovative Research (AcSIR))
- Shivani Chitkara
(Academy of Scientific and Innovative Research (AcSIR))
- Tripti Nair
(Aruna Asaf Ali Marg
University of Southern California)
- Rachamadugu Sai Keerthana
(Aruna Asaf Ali Marg)
- Shantanu Sengupta
(CSIR-Institute of Genomics and Integrative Biology
Academy of Scientific and Innovative Research (AcSIR))
- Arnab Mukhopadhyay
(Aruna Asaf Ali Marg)
Abstract
The folate and methionine cycles (Met-C) are regulated by vitamin B12 (B12), obtained exclusively from diet and microbiota. Met-C supports amino acid, nucleotide, and lipid biosynthesis and provides one-carbon moieties for methylation reactions. While B12 deficiency and polymorphisms in Met-C genes are clinically attributed to neurological and metabolic disorders, less is known about their cell-non-autonomous regulation of systemic physiological processes. Using a B12-sensitive Caenorhabditis elegans mutant, we show that the neuronal Met-C responds to differential B12 content in diet to regulate p38-MAPK activation in the intestine, thereby modulating cytoprotective gene expression, osmotic stress tolerance, behaviour and longevity. Mechanistically, our data suggest that B12-driven changes in the metabolic flux through the Met-C in the mutant’s serotonergic neurons increase serotonin biosynthesis. Serotonin activates its receptor, MOD-1, in the post-synaptic interneurons, which then secretes the neuropeptide FLR-2. FLR-2 binding to its intestinal receptor, FSHR-1, induces the phase transition of the SARM domain protein TIR-1, thereby activating the p38-MAPK pathway. Together, we reveal a dynamic neuron-gut signalling axis that helps an organism modulate life history traits based on the status of neuronal Met-C, determined by B12 availability in its diet.
Suggested Citation
Sabnam Sahin Rahman & Shreya Bhattacharjee & Simran Motwani & Govind Prakash & Rajat Ujjainiya & Shivani Chitkara & Tripti Nair & Rachamadugu Sai Keerthana & Shantanu Sengupta & Arnab Mukhopadhyay, 2025.
"Methionine cycle in C. elegans serotonergic neurons regulates diet-dependent behaviour and longevity through neuron-gut signaling,"
Nature Communications, Nature, vol. 16(1), pages 1-20, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60475-0
DOI: 10.1038/s41467-025-60475-0
Download full text from publisher
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:16:y:2025:i:1:d:10.1038_s41467-025-60475-0. 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.
We have no bibliographic references for this item. You can help adding them by using 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.