ArticleNature cell biology2024
Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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The trial behind it
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Who cites it
81 citing papers in PubMed.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Exploring regulated cell death in renal cell carcinoma: mechanistic insights and therapeutic perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Decoding the metabolic‑immune crosstalk: The role of glutamine and ammonium reprogramming in prostate cancer immune evasion (Review).Oncology reports · 2026Review
- Hyperuricemia increases susceptibility to chronic kidney injury exacerbation via autophagic flux blockade-mediated ammonia death pathway.Journal of advanced research · 2026Article
- Ammonia Accumulation Drives Intervertebral Disc Degeneration by Triggering Ammonia-Induced Cell Death Through Lysosome-Mitochondria Crosstalk.Cell proliferation · 2026Article
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Ammonia-induced cell death patterns in glioblastoma: Immune landscape, prognostic signature, and therapeutic target identification.Genes & diseases · 2026Article
- Article
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Insights into programmed cell death from multiple imaging modalities.Journal of translational medicine · 2026Review
- AMPK Suppresses Multiple Forms of Cell Death Including Disulfidptosis in Tumor-Associated Macrophages During Tumor Progression.International journal of molecular sciences · 2026Article
- Metabolic dysfunction-associated steatohepatitis exacerbated by Clostridium perfringens-derived ammonia is attenuated by tripeptide DT-109.The Journal of clinical investigation · 2026Article
- Ammonia in the crosshairs: microbial targets for metabolic dysfunction-associated steatohepatitis prevention.The Journal of clinical investigation · 2026Article
- Diversion of Arginine's dietary metabolic fate in proteinuric kidney disease.Research square · 2026Article
- Protein arginine methyltransferase 5 orchestrates the homeostasis and reconstitution of intestinal stem cell niche via balancing urea cycling.Cell communication and signaling : CCS · 2026Article
- Ammonia Detoxification Inhibits Liver Metastasis by Reshaping Hepatic Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Ammonia is thought to be a cytotoxin and its increase in the blood impairs cell function. However, whether and how this toxin triggers cell death under pathophysiological conditions remains unclear. Here we show that ammonia induces a distinct form of cell death in effector T cells. We found that rapidly proliferating T cells use glutaminolysis to release ammonia in the mitochondria, which is then translocated to and stored in the lysosomes. Excessive ammonia accumulation increases lysosomal pH and results in the termination of lysosomal ammonia storage and ammonia reflux into mitochondria, leading to mitochondrial damage and cell death, which is characterized by lysosomal alkalization, mitochondrial swelling and impaired autophagic flux. Inhibition of glutaminolysis or blocking lysosomal alkalization prevents ammonia-induced T cell death and improves T cell-based antitumour immunotherapy. These findings identify a distinct form of cell death that differs from previously known mechanisms.
Indexed as
Identifiers
39261719What OpenQuestion holds
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.