ArticlePLoS genetics2020
A conserved role for AMP-activated protein kinase in NGLY1 deficiency.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Cytosolic Peptide: N-Glycanase (NGLY1)-from Basic Biology to Genetic Disorder, NGLY1 Deficiency.Advances in experimental medicine and biology · 2026Review
- The STING pathway drives noninflammatory neurodegeneration in NGLY1 deficiency.The Journal of experimental medicine · 2025Article
- NGLY1 deficiency - clinical features and therapeutic strategy.Journal of human genetics · 2025Review
- Increased oxidative stress and autophagy in NGLY1 patient iPSC-derived neural stem cells.Experimental cell research · 2025Article
- Systemic gene therapy corrects the neurological phenotype in a mouse model of NGLY1 deficiency.JCI insight · 2024Article
- Development of new NGLY1 assay systems - toward developing an early screening method for NGLY1 deficiency.Glycobiology · 2024Review
- Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans.PLoS biology · 2024Article
- Development of a fluorescence and quencher-based FRET assay for detection of endogenous peptide:N-glycanase/NGLY1 activity.The Journal of biological chemistry · 2024Article
- NGLY1 mutations cause protein aggregation in human neurons.Cell reports · 2023Article
- Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila.Nature communications · 2023Article
- Generation and characterization of NGLY1 patient-derived midbrain organoids.Frontiers in cell and developmental biology · 2023Article
- Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.Nutrients · 2022Review
- NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.Cells · 2022Review
- Ferroptosis regulation by the NGLY1/NFE2L1 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Tracing the NGLY1 footprints: insights from Drosophila.Journal of biochemistry · 2022Review
- Review
- Regulation of mitochondrial cargo-selective autophagy by posttranslational modifications.The Journal of biological chemistry · 2021Review
- An induced pluripotent stem cell line (NCATS-CL9075) from a patient carrying compound heterozygote mutations, p.R390P and p.L318P, in the NGLY1 gene.Stem cell research · 2021Article
- Reversibility of motor dysfunction in the rat model of NGLY1 deficiency.Molecular brain · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in human N-glycanase 1 (NGLY1) cause the first known congenital disorder of deglycosylation (CDDG). Patients with this rare disease, which is also known as NGLY1 deficiency, exhibit global developmental delay and other phenotypes including neuropathy, movement disorder, and constipation. NGLY1 is known to regulate proteasomal and mitophagy gene expression through activation of a transcription factor called "nuclear factor erythroid 2-like 1" (NFE2L1). Loss of NGLY1 has also been shown to impair energy metabolism, but the molecular basis for this phenotype and its in vivo consequences are not well understood. Using a combination of genetic studies, imaging, and biochemical assays, here we report that loss of NGLY1 in the visceral muscle of the Drosophila larval intestine results in a severe reduction in the level of AMP-activated protein kinase α (AMPKα), leading to energy metabolism defects, impaired gut peristalsis, failure to empty the gut, and animal lethality. Ngly1-/- mouse embryonic fibroblasts and NGLY1 deficiency patient fibroblasts also show reduced AMPKα levels. Moreover, pharmacological activation of AMPK signaling significantly suppressed the energy metabolism defects in these cells. Importantly, the reduced AMPKα level and impaired energy metabolism observed in NGLY1 deficiency models are not caused by the loss of NFE2L1 activity. Taken together, these observations identify reduced AMPK signaling as a conserved mediator of energy metabolism defects in NGLY1 deficiency and suggest AMPK signaling as a therapeutic target in this disease.
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