RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis.
4 affiliations
- 1Molecular Aging Laboratory, National Institute of Immunology, Delhi, India.
- 2CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
- 3Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
- 4Molecular Aging Laboratory, National Institute of Immunology, Delhi, India. [email protected].
Abstract
Adaptive modulation of physiological traits in response to dietary fluctuations is essential for organismal fitness and is governed by complex gene-diet interactions that remain mechanistically unexplored. Here, we identify the conserved mTORC2 component RICTOR as a critical regulator of dietary plasticity in Caenorhabditis elegans. Loss of rict-1/RICTOR confers enhanced osmotic stress tolerance and longevity on vitamin B12-rich bacterial diets containing optimal methionine. These adaptations require two B12-dependent enzymes: methionine synthase (METR-1), functioning in the one-carbon cycle (Met-C), and methylmalonyl-CoA mutase (MMCM-1), a mitochondrial enzyme essential for propionate catabolism which generates succinyl-CoA, and via the TCA cycle, succinate. Elevated succinate induces mitochondrial fragmentation, activating mitophagy that is indispensable for the stress resilience and longevity of rict-1 mutant worms. This host Met-C-mitophagy axis is tuned by microbial inputs, constituting an interspecies interaction. Early-life fragmentation potentiates sustained mitophagy into late adulthood, preserving tubular mitochondria as the rict-1 mutant worms age, unlike wild-type worms. Thus, RICTOR restrains host sensitivity to microbe-derived metabolite fluctuations through organellar quality control, regulating lifespan.
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BibTeX
@article{motwani2026rictor,
title = {{RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis.}},
author = {Simran Motwani and Somya Bhandari and Shivani Chitkara and Rajat Ujjainiya and Prerona Ghosh and Shantanu Sengupta and Arnab Mukhopadhyay},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77722-7},
url = {https://europepmc.org/article/MED/42967947},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis.
AU - Simran Motwani
AU - Somya Bhandari
AU - Shivani Chitkara
AU - Rajat Ujjainiya
AU - Prerona Ghosh
AU - Shantanu Sengupta
AU - Arnab Mukhopadhyay
PY - 2026
DA - 2026/09/14
JO - Nature communications
DO - 10.1038/s41467-026-77722-7
UR - https://europepmc.org/article/MED/42967947
AB - Adaptive modulation of physiological traits in response to dietary fluctuations is essential for organismal fitness and is governed by complex gene-diet interactions that remain mechanistically unexplored. Here, we identify the conserved mTORC2 component RICTOR as a critical regulator of dietary plasticity in Caenorhabditis elegans. Loss of rict-1/RICTOR confers enhanced osmotic stress tolerance and longevity on vitamin B12-rich bacterial diets containing optimal methionine. These adaptations require two B12-dependent enzymes: methionine synthase (METR-1), functioning in the one-carbon cycle (Met-C), and methylmalonyl-CoA mutase (MMCM-1), a mitochondrial enzyme essential for propionate catabolism which generates succinyl-CoA, and via the TCA cycle, succinate. Elevated succinate induces mitochondrial fragmentation, activating mitophagy that is indispensable for the stress resilience and longevity of rict-1 mutant worms. This host Met-C-mitophagy axis is tuned by microbial inputs, constituting an interspecies interaction. Early-life fragmentation potentiates sustained mitophagy into late adulthood, preserving tubular mitochondria as the rict-1 mutant worms age, unlike wild-type worms. Thus, RICTOR restrains host sensitivity to microbe-derived metabolite fluctuations through organellar quality control, regulating lifespan.
SN - 2041-1723
ER -