ArticleAutophagy2017
Autophagy impairment mediated by S-nitrosation of ATG4B leads to neurotoxicity in response to hyperglycemia.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 104 citations in OpenAlex.
- Review
- S-nitrosoglutathione reductase GSNOR drives age-related obesity by promoting adipose tissue whitening through de-nitrosation of Beclin-1.Nature communications · 2026Article
- Hydrogen peroxide as a multifaceted regulator of the Atg4 protease and autophagy in the pathogenic fungusFrontiers in fungal biology · 2026Article
- Loss of Atoh8 Impairs Macroautophagy.Cells · 2025Article
- Review
- Protective Role of Spermidine Against Diabetes-Induced Ovarian and Endometrial Injury via LC3 and Beclin-1 Modulation.Antioxidants (Basel, Switzerland) · 2025Article
- Nitric oxide‑mediated S‑Nitrosylation contributes to signaling transduction in human physiological and pathological status (Review).International journal of molecular medicine · 2025Review
- Acute high glucose exposure impairs synaptosomal vesicle release activity.Brain research · 2025Article
- Identification of Lipophagy-Related Gene Signature for Diagnosis and Risk Prediction of Alzheimer's Disease.Biomedicines · 2025Article
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Diabetic encephalopathy: metabolic reprogramming as a potential driver of accelerated brain aging and cognitive decline.Frontiers in cell and developmental biology · 2025Review
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Article
- Recent Advances in Biomolecular Patho-Mechanistic Pathways behind the Development and Progression of Diabetic Neuropathy.Biomedicines · 2024Review
- The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024Review
- UBE3C tunes autophagy via ATG4B ubiquitination.Autophagy · 2024Article
- Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Nitric oxide-induced lipophagic defects contribute to testosterone deficiency in rats with spinal cord injury.Frontiers in endocrinology · 2024Article
- Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.Cell death & disease · 2023Article
- S-Nitrosylated Proteins Involved in Autophagy inLife (Basel, Switzerland) · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of diabetic patients develop neuropathy and there is an increasing prevalence of neurodegeneration in the central nervous system (CNS). However, the mechanism behind this is poorly understood. Here we first observed that macroautophagy/autophagy was suppressed in the hippocampus of diabetic GK rats with hyperglycemia, whereas it was unchanged in ob/ob mice without hyperglycemia. Autophagy could be directly inhibited by high glucose in mouse primary hippocampal neurons. Moreover, autophagy was protective in high-glucose-induced neurotoxicity. Further studies revealed that autophagic flux was suppressed by high glucose due to impaired autophagosome synthesis illustrated by mRFP-GFP-LC3 puncta analysis. We showed that decreased autophagy was dependent on NO produced under high glucose conditions. Therefore, (LC-MS/MS)-based quantitative proteomic analysis of protein S-nitrosation was performed and a core autophagy protein, ATG4B was found to be S-nitrosated in the hippocampus of GK rats. ATG4B was also verified to be S-nitrosated in neuronal cells cultured with high glucose. The activities of ATG4B in the processing of unmodified, precursor Atg8-family proteins and in the deconjugation of PE from lipidated Atg8-family proteins, which are essential for efficient autophagosome biogenesis were both compromised by S-nitrosation at Cys189 and Cys292 sites. In addition, ATG4B processing of the GABARAPL1 precursor was affected the least by S-nitrosation compared with other substrates. Finally, ATG4B S-nitrosation was verified to be responsible for decreased autophagy and neurotoxicity in response to high glucose. In conclusion, autophagy impairment mediated by S-nitrosation of ATG4B leads to neurotoxicity in response to hyperglycemia. Our research reveals a novel mechanism linking hyperglycemia with CNS neurotoxicity and shows that S-nitrosation is a novel post-transcriptional modification of the core autophagy machinery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.