ArticleAging cell2018
NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed.
- An atlas of thebioRxiv : the preprint server for biology · 2026Article
- Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut-brain signaling in Caenorhabditis elegans.PLoS biology · 2026Article
- A somatic checkpoint through NHR-49/HNF4α governs reproductive investment and longevity in C. elegans.Nature communications · 2026Article
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- Article
- Mild Mitochondrial Impairment Activates Overlapping Longevity Pathways Converging on the Flavin-Containing Monooxygenase FMO-2.bioRxiv : the preprint server for biology · 2026Article
- Mild mitochondrial impairment activates overlapping longevity pathways converging on the flavin-containing monooxygenase FMO-2.Frontiers in aging · 2026Article
- A gut-activated NHR-86-CYP pathway mediates the neuroprotective effects of Enterococcus faecium probiotics in a nematode model of amyotrophic lateral sclerosis.PLoS biology · 2026Article
- Gastrodin extends the lifespan of Caenorhabditis elegans via the DAF-16/FOXO signaling pathway and autophagy.Functional & integrative genomics · 2025Article
- Bacterial exopolysaccharides mediate activation of flavin-containing monooxygenase 2 to extend lifespan in Caenorhabditis elegans.Cell communication and signaling : CCS · 2025Article
- Phenotypic and metabonomics studies of FMOs in C. elegans and their roles in lifespan extension.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Human gut Bifidobacteria strains regulate host longevity via shared and divergent mechanisms inbioRxiv : the preprint server for biology · 2025Article
- Lactate promotes longevity through redox-driven lipid remodeling inbioRxiv : the preprint server for biology · 2025Article
- Nuclear Hormone Receptor NHR-49/HNF4α Couples Fertility Regulation to Resource Allocation and Longevity inbioRxiv : the preprint server for biology · 2025Article
- Curcumin enhances the anti-obesogenic activity of orlistat through SKN-1/NRF2-dependent regulation of nutrient metabolism in Caenorhabditis elegans.International journal of obesity (2005) · 2025Article
- Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans.Nature communications · 2025Article
- MONITTR allows real-time imaging of transcription and endogenous proteins in C. elegans.The Journal of cell biology · 2025Article
- Perception ofmicroPublication biology · 2025Article
- Transcriptional coactivator MED15 is required for beta cell maturation.Nature communications · 2024Article
- Free long-chain fatty acids trigger early postembryonic development in starved Caenorhabditis elegans by suppressing mTORC1.PLoS biology · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Endogenous and exogenous stresses elicit transcriptional responses that limit damage and promote cell/organismal survival. Like its mammalian counterparts, hepatocyte nuclear factor 4 (HNF4) and peroxisome proliferator-activated receptor α (PPARα), Caenorhabditis elegans NHR-49 is a well-established regulator of lipid metabolism. Here, we reveal that NHR-49 is essential to activate a transcriptional response common to organic peroxide and fasting, which includes the pro-longevity gene fmo-2/flavin-containing monooxygenase. These NHR-49-dependent, stress-responsive genes are also upregulated in long-lived glp-1/notch receptor mutants, with two of them making critical contributions to the oxidative stress resistance of wild-type and long-lived glp-1 mutants worms. Similar to its role in lipid metabolism, NHR-49 requires the mediator subunit mdt-15 to promote stress-induced gene expression. However, NHR-49 acts independently from the transcription factor hlh-30/TFEB that also promotes fmo-2 expression. We show that activation of the p38 MAPK, PMK-1, which is important for adaptation to a variety of stresses, is also important for peroxide-induced expression of a subset of NHR-49-dependent genes that includes fmo-2. However, organic peroxide increases NHR-49 protein levels, by a posttranscriptional mechanism that does not require PMK-1 activation. Together, these findings establish a new role for the HNF4/PPARα-related NHR-49 as a stress-activated regulator of cytoprotective gene expression.
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