Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response
Open accessAbstract
Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus.
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With relative ease, dietary and genetic influences can be simultaneously investigated in C. elegans.
“With relative ease, dietary and genetic influences can be simultaneously investigated in C. elegans (298).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [298]
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“Hence, DA1877 can induce whole-scale metabolic responses in the worm to modulate development and aging (Watson et al., 2013) (Figure 1D).”
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- Authors
- Watson, E., MacNeil, L. T., Arda, H. E., Zhu, L. J., & Walhout, A. J. M.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Walhout, Albertha J.M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 153
- Issue
- 1
- Pages
- 253-266
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3817025
- OpenAlex
- W2080908567
- Cited by
- 134
- References
- 40
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 6 · 2020: 11 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 6
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-06-06)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK068429, DK068429, R01DK068429)
- National Center for Research Resources
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- Caenorhabditis elegans, dietary response, metabolic networks, gene regulatory networks, mitochondrial metabolism, amino acid metabolism, TCA cycle, transcription factors, amino acid metabolism disorders, dietary intervention
- MeSH terms
- Animals, Diet, Escherichia coli, Humans, Insulin, Metabolism, Inborn Errors, Mitochondria, Transcription Factors, Signal Transduction, Caenorhabditis elegans, Phosphotransferases (Alcohol Group Acceptor), Betaproteobacteria, Caenorhabditis elegans Proteins, RNA Interference, Acyl-CoA Dehydrogenase, Gene Regulatory Networks, Metabolic Networks and Pathways
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