ArticleProceedings of the National Academy of Sciences of the United States of America2014
Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses that pooled it.
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Who cites it
93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 198 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Trial
- Arginine deprivation induces prolonged autophagy activation and ROS-dependent cell death in glioblastoma multiforme.CNS oncology · 2026Article
- Cysteine metabolism dysregulation promotes ferroptosis in osteoarthritis: Insights from multi-species bioinformatics and experimental validation.Journal of orthopaedic translation · 2026Article
- Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.Human cell · 2026Article
- Adaptive crosstalk between polyamine metabolism, translation, and autophagy sustains energy homeostasis in mammals during starvation: a scoping review.Amino acids · 2026Review
- Solute carrier family (SLC) amino acid transporters are upregulated in cutaneous squamous cell carcinoma.Biology direct · 2026Article
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Autophagy is an upstream mediator of chromatin dynamics in normal and autoimmune germinal center B cells.The Journal of clinical investigation · 2025Article
- Mammalian nucleophagy: process and function.Autophagy · 2025Review
- Adaptation to Arginine Deprivation Leads to a More Aggressive, Therapy-Resistant Phenotype in HNSCC Cells.Biomolecules · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- BCL-XL Protects ASS1-Deficient Cancers from Arginine Starvation-Induced Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- Quantifying glucose uptake at the single cell level with confocal microscopy reveals significant variability within and across individuals.Scientific reports · 2025Article
- Cellular Signaling of Amino Acid Metabolism in Prostate Cancer.International journal of molecular sciences · 2025Review
- Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- In Vivo Monitoring of Nucleophagy in Caenorhabditis elegans.Methods in molecular biology (Clifton, N.J.) · 2024Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone-associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments.
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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.