ArticlePloS one2016
Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Integrative study revealsWorld journal of gastroenterology · 2026Article
- Ammonia signaling network: the intersection of tumor metabolism, epigenetics, and metastasis.Frontiers in endocrinology · 2026Review
- Ammonia in cancer: dual roles and therapeutic strategies.Cancer cell international · 2025Review
- Novel roles of ammonia in physiology and cancer.Journal of molecular cell biology · 2025Review
- Low extracellular pH protects cancer cells from ammonia toxicity.Cell death discovery · 2025Article
- β-Catenin/c-Myc Axis Modulates Autophagy Response to Different Ammonia Concentrations.Advanced biology · 2025Article
- Sirtuin 5 alleviates apoptosis and autophagy stimulated by ammonium chloride in bovine mammary epithelial cells.Experimental and therapeutic medicine · 2024Article
- Dopamine receptor D3 is related to prognosis in human hepatocellular carcinoma and inhibits tumor growth.BMC cancer · 2022Article
- Ammonia induces amyloidogenesis in astrocytes by promoting amyloid precursor protein translocation into the endoplasmic reticulum.The Journal of biological chemistry · 2022Article
- G-Protein Coupled Receptor Signaling and Mammalian Target of Rapamycin Complex 1 Regulation.Molecular pharmacology · 2022Review
- Dopamine D3 receptor signaling alleviates mouse rheumatoid arthritis by promoting Toll-like receptor 4 degradation in mast cells.Cell death & disease · 2022Article
- Dopamine DHypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Reversible Treatment of Pressure Overload-Induced Left Ventricular Hypertrophy throughAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- ULK1 inhibitor induces spindle microtubule disorganization and inhibits phosphorylation of Ser10 of histone H3.FEBS open bio · 2020Article
- ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle.PLoS biology · 2020Article
- Hepatic encephalopathy is linked to alterations of autophagic flux in astrocytes.EBioMedicine · 2019Article
- The Prospective Value of Dopamine Receptors on Bio-Behavior of Tumor.Journal of Cancer · 2019Review
- Lysosomotropic drugs activate TFEB via lysosomal membrane fluidization and consequent inhibition of mTORC1 activity.Cell death & disease · 2018Article
- Triptolide induces protective autophagy and apoptosis in human cervical cancer cells by downregulating Akt/mTOR activation.Oncology letters · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperammonemia is frequently seen in tumor microenvironments as well as in liver diseases where it can lead to severe brain damage or death. Ammonia induces autophagy, a mechanism that tumor cells may use to protect themselves from external stresses. However, how cells sense ammonia has been unclear. Here we show that culture medium alone containing Glutamine can generate milimolar of ammonia at 37 degrees in the absence of cells. In addition, we reveal that ammonia acts through the G protein-coupled receptor DRD3 (Dopamine receptor D3) to induce autophagy. At the same time, ammonia induces DRD3 degradation, which involves PIK3C3/VPS34-dependent pathways. Ammonia inhibits MTOR (mechanistic target of Rapamycin) activity and localization in cells, which is mediated by DRD3. Therefore, ammonia has dual roles in autophagy: one to induce autophagy through DRD3 and MTOR, the other to increase autophagosomal pH to inhibit autophagic flux. Our study not only adds a new sensing and output pathway for DRD3 that bridges ammonia sensing and autophagy induction, but also provides potential mechanisms for the clinical consequences of hyperammonemia in brain damage, neurodegenerative diseases and tumors.
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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 OpenQuestion graph.