ArticleNature communications2023
Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- Atg2 coordinates microbial metabolite signaling and epigenetic remodeling to maintain intestinal lipid homeostasis in Drosophila.Microbiome · 2026Article
- The Drosophila proventriculus lacks stem cells but compensates for age-related cell loss via endoreplication-mediated cell growth.Nature communications · 2026Article
- Cytosolic Peptide: N-Glycanase (NGLY1)-from Basic Biology to Genetic Disorder, NGLY1 Deficiency.Advances in experimental medicine and biology · 2026Review
- Linking the production of reactive oxygen species to the expression of antimicrobial peptides through aquaporin in an arthropod.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NGLY1 deficiency - clinical features and therapeutic strategy.Journal of human genetics · 2025Review
- Impaired Proteostasis is Linked to Neurological Pathology in a Zebrafish NGLY1 Deficiency Model.Journal of inherited metabolic disease · 2025Article
- Article
- Bifidobacterium longum NSP001-derived extracellular vesicles ameliorate ulcerative colitis by modulating T cell responses in gut microbiota-(in)dependent manners.NPJ biofilms and microbiomes · 2025Article
- Proteomic analysis across aged tissues reveals distinct signatures and the crucial involvement of midgut barrier function in the regulation of aging.Aging cell · 2025Article
- Identification of AS1842856 as a novel small-molecule GSK3α/β inhibitor against Tauopathy by accelerating GSK3α/β exocytosis.Aging cell · 2025Article
- Vitamin B12 ameliorates gut epithelial injury via modulating the HIF-1 pathway and gut microbiota.Cellular and molecular life sciences : CMLS · 2024Article
- Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans.PLoS biology · 2024Article
- Novel Insights into the circRNA-Modulated Developmental Mechanism of Western Honey Bee Larval Guts.Insects · 2023Article
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9 authors at 3 institutions in 3 countries.
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Abstract
Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not lethality. However, raising Pngl mutants on isocaloric, fat-rich diets partially rescued lethality. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the lethality caused by loss of Pngl is primarily mediated through non-bacterial induction of immune and metabolic abnormalities.
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