ArticleNature metabolism2025
NUFIP1 integrates amino acid sensing and DNA damage response to maintain the intestinal homeostasis.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Soluble Dietary Fiber fromInternational journal of molecular sciences · 2026Article
- The C2H2-GGAT Regulatory Module Fine-Tunes Glutamate Homeostasis to Improve Fruit Flavour and Enhance Disease Resistance in Peach.Plant biotechnology journal · 2026Article
- NUFIP1-engineered exosomes modulate propofol-induced neurotoxicity in neonatal rats via the ERS apoptotic pathway.Apoptosis : an international journal on programmed cell death · 2026Article
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- Intestinal amino acid metabolic response and its roles in inflammatory bowel disease.Cell communication and signaling : CCS · 2025Review
- NUFIP1 at the crossroads of ribophagy and disease: unveiling therapeutic implications.Journal of translational medicine · 2025Review
- Curcumin for inflammatory bowel disease therapy: advances in mechanisms, clinical applications, and drug delivery.Archives of pharmacal research · 2025Review
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Features and mechanisms of long-livedZoological research · 2025Article
- Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy regulates immune function of dendritic cells in polymicrobial sepsis.Burns & trauma · 2025Article
- Association between the dietary index for gut microbiota and Alzheimer's disease: A cross-sectional study from the National Health and Nutrition Examination Survey (2004 to 2018).Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
11 authors.
Funding
Abstract
Nutrient availability strongly affects intestinal homeostasis. Here, we report that low-protein (LP) diets decrease amino acids levels, impair the DNA damage response (DDR), cause DNA damage and exacerbate inflammation in intestinal tissues of male mice with inflammatory bowel disease (IBD). Intriguingly, loss of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1) contributes to the amino acid deficiency-induced impairment of the DDR in vivo and in vitro and induces necroptosis-related spontaneous enteritis. Mechanistically, phosphorylated NUFIP1 binds to replication protein A2 (RPA32) to recruit the ataxia telangiectasia and Rad3-related (ATR)-ATR-interacting protein (ATRIP) complex, triggering the DDR. Consistently, both reintroducing NUFIP1 but not its non-phospho-mutant and inhibition of necroptosis prevent bowel inflammation in male Nufip1 conditional knockout mice. Intestinal inflammation and DNA damage in male mice with IBD can be mitigated by NUFIP1 overexpression. Moreover, NUFIP1 protein levels in the intestine of patients with IBD were found to be significantly decreased. Conclusively, our study uncovers that LP diets contribute to intestinal inflammation by hijacking NUFIP1-DDR signalling and thereby activating necroptosis.
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Registered trials
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