Related Experiment Video
Updated: Sep 11, 2025
09:18
Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
Published on: September 7, 2021
3.0K
RICTOR regulates an interspecies crosstalk that influences longevity through a novel methionine cycle-mitophagy axis
Simran Motwani1, Somya Bhandari1, Shivani Chitkara2
1Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Biorxiv : the Preprint Server for Biology
|August 12, 2025
Summary
The mechanistic target of rapamycin complex 2 (mTORC2) component RICTOR regulates dietary plasticity in response to vitamin B12. Loss of RICTOR enhances stress tolerance and longevity by linking the folate-methionine cycle to mitophagy.
Area of Science:
- Molecular biology
- Genetics
- Metabolism
Background:
- Organismal fitness depends on adapting physiological traits to environmental variability, especially diet.
- Gene-diet interactions are key, but molecular links between microbial metabolites and host pathways are underexplored.
Purpose of the Study:
- Identify regulators of dietary plasticity in response to microbial metabolites.
- Investigate the role of RICTOR in integrating nutrient signals with host stress response and metabolism.
Main Methods:
- Utilized *Caenorhabditis elegans* as a model organism.
- Investigated gene-diet interactions involving vitamin B12 and RICTOR.
- Analyzed B12-dependent enzymes (methionine synthase, methylmalonyl-CoA mutase) and their downstream effects.
Main Results:
- Loss of *rict-1* (RICTOR ortholog) enhances osmotic stress tolerance and longevity on vitamin B12-rich diets.
- Phenotypic adaptations require methionine synthase and methylmalonyl-CoA mutase.
- Elevated succinate from propionate catabolism induces mitophagy, crucial for stress resilience and longevity.
- A methionine synthase-mitophagy axis is modulated by microbial vitamin B12 and methionine.
Conclusions:
- RICTOR restrains host sensitivity to microbial metabolites, maintaining mitochondrial homeostasis and regulating lifespan.
- RICTOR plays a pivotal role in insulating host physiology from nutrient-driven perturbations via organellar quality control.
- Identified a conserved pathway linking microbial metabolites, host metabolism, and longevity through RICTOR and mitophagy.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
01:37Mitochondria
14.9K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
14.9K
01:46Electron Transport Chain: Complex I and II
15.0K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
15.0K
01:19Translocation of Proteins into the Mitochondria
3.2K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K
01:22PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K
01:31Regulation of the Unfolded Protein Response
2.6K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K