ArticleInternational journal of molecular sciences2023
Arginine Expedites Erastin-Induced Ferroptosis through Fumarate.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Mitochondrial hub: the integrative axis connecting ferroptosis and metabolic reprogramming in periodontitis.Molecular biology reports · 2026Review
- C-terminal interleukin 1 alpha (IL-1α) overexpression drives EMT and a vulnerability to ferroptosis in HNSCC.Redox biology · 2026Article
- The Dietary Polyphenol Resveratrol in Intestinal Ischemia-Reperfusion Injury: From Multifaceted Protective Mechanisms to Clinical Translation Challenges.Food science & nutrition · 2026Review
- Ferroptosis reshapes the tumor immune microenvironment: molecular mechanisms, immune regulation, and therapeutic synergistic strategies.Frontiers in immunology · 2026Review
- Inhibition of Ferroptosis Attenuates Neuron Damage and Improves Cognitive Impairment in Mice Surviving Severe Hypothermia.International journal of molecular sciences · 2025Article
- Mechanism of Lipi Jiangzhuo Decoction in Improving Metabolic Dysfunction-Associated Steatohepatitis Through the PERK/PINK1/GPx4 Pathway.Journal of inflammation research · 2025Article
- Serum Metabolomic Signatures of Dyslipidemia in Narcolepsy Type 1: A Multi-Center Cross-Sectional Study.Nature and science of sleep · 2025Article
- The Causal Association Analysis between Depression and Cerebrospinal Fluid: From the Perspective of Mendelian Randomization.Psychology research and behavior management · 2025Article
- An iron-containing nanomedicine for inducing deep tumor penetration and synergistic ferroptosis in enhanced pancreatic cancer therapy.Materials today. Bio · 2024Article
- Ferroptosis: a promising target for fumarate hydratase-deficient tumor therapeutics literature review.Translational cancer research · 2024Review
- Integrating Genome-Scale Metabolic Models with Patient Plasma Metabolome to Study Endothelial Metabolism In Situ.International journal of molecular sciences · 2024Article
- Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome.Frontiers in molecular biosciences · 2024Article
- Ferroptosis at the nexus of metabolism and metabolic diseases.Theranostics · 2024Review
- Immunometabolism of ferroptosis in the tumor microenvironment.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ferroptosis is a newly characterized form of programmed cell death. The fundamental biochemical feature of ferroptosis is the lethal accumulation of iron-catalyzed lipid peroxidation. It has gradually been recognized that ferroptosis is implicated in the pathogenesis of a variety of human diseases. Increasing evidence has shed light on ferroptosis regulation by amino acid metabolism. Herein, we report that arginine deprivation potently inhibits erastin-induced ferroptosis, but not RSL3-induced ferroptosis, in several types of mammalian cells. Arginine presence reduces the intracellular glutathione (GSH) level by sustaining the biosynthesis of fumarate, which functions as a reactive α,β-unsaturated electrophilic metabolite and covalently binds to GSH to generate succinicGSH. siRNA-mediated knockdown of argininosuccinate lyase, the critical urea cycle enzyme directly catalyzing the biosynthesis of fumarate, significantly decreases cellular fumarate and thus relieves erastin-induced ferroptosis in the presence of arginine. Furthermore, fumarate is decreased during erastin exposure, suggesting that a protective mechanism exists to decelerate GSH depletion in response to pro-ferroptotic insult. Collectively, this study reveals the ferroptosis regulation by the arginine metabolism and expands the biochemical functionalities of arginine.
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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.