RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis
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Updated: Nov 3, 2026

The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan
Published on: June 29, 2018
Simran Motwani1, Somya Bhandari1, Shivani Chitkara2
1Molecular Aging Laboratory, National Institute of Immunology, Delhi, India.
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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