ArticleCell death & disease2022
The interaction between STING and NCOA4 exacerbates lethal sepsis by orchestrating ferroptosis and inflammatory responses in macrophages.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 163 citations in OpenAlex.
- Ferroptosis in heatstroke: Mechanisms and therapeutic perspectives (Review).International journal of molecular medicine · 2026Review
- GEF-H1 upon microtubule destabilization drives ZBP1-dependent necroptosis.Cell death and differentiation · 2026Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Role of PRMT5 in regulating ferritinophagy during Mycobacterium tuberculosis infection.PLoS pathogens · 2026Article
- C3aR inhibition alleviates cerebral ischemia-reperfusion injury via STING-mediated ferroptosis through SLC7A11/GPX4.iScience · 2026Article
- Targeting FAR1 to inhibit intestinal macrophage ferroptosis: repurposing irinotecan as a novel sepsis therapy.Apoptosis : an international journal on programmed cell death · 2026Article
- hsa_circ_0006156 Suppresses Malignant Progression by Inducing Ferroptosis in Gastric Cancer Via miR-942-5p/NCOA4 Axis.Biochemical genetics · 2026Article
- Ferroptosis-related TFRC: a potential therapeutic target in sepsis and regulatory effect of γ-Tocotrienol.Human genomics · 2026Article
- The emerging Nexus of STING signaling and ferroptosis: from mechanisms to therapeutic opportunities.Cell death discovery · 2026Review
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Ferroptosis as an approach to leverage cancer metabolism.Trends in cell biology · 2026Review
- Exploring the Therapeutic Potential of Ganoderic Acid A Against Inflammatory Bowel Disease Based on Network Pharmacology, Molecular Docking, and Intestinal Organoid Validation.International journal of molecular sciences · 2026Article
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- BZW1 Drives Immune Evasion in Lung Adenocarcinoma via Ferroptosis Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AgJournal of nanobiotechnology · 2026Article
- Mitochondria-driven ferroptosis in intervertebral disc degeneration: A novel target in age-related spinal diseases (Review).Experimental and therapeutic medicine · 2026Review
- Polystyrene nanoplastics and benzo(a)pyrene synergistically induce lung fibrosis and inflammation via relaxin signalling in mice.Communications biology · 2026Article
- Polyethylene terephthalate microplastics impair erectile function through macrophage mediated cGAS-STING ferroptosis.iScience · 2026Article
- STING-ERO1 signaling exacerbates PARylation-mediated parthanatos in sepsis.Cell communication and signaling : CCS · 2026Article
- α-synuclein triggers NCOA4-FTH1-mediated ferroptosis of oligodendrocyte in multiple system atrophy.Acta neuropathologica · 2026Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery of STING-related innate immunity has recently provided a deep mechanistic understanding of immunopathy. While the detrimental effects of STING during sepsis had been well documented, the exact mechanism by which STING causes lethal sepsis remains obscure. Through single-cell RNA sequence, genetic approaches, and mass spectrometry, we demonstrate that STING promotes sepsis-induced multiple organ injury by inducing macrophage ferroptosis in a cGAS- and interferon-independent manner. Mechanistically, Q237, E316, and S322 in the CBD domain of STING are critical binding sites for the interaction with the coiled-coil domain of NCOA4. Their interaction not only triggers ferritinophagy-mediated ferroptosis, but also maintains the stability of STING dimers leading to enhanced inflammatory response, and reduces the nuclear localization of NCOA4, which impairs the transcription factor coregulator function of NCOA4. Meanwhile, we identified HET0016 by high throughput screening, a selective 20-HETE synthase inhibitor, decreased STING-induced ferroptosis in peripheral blood mononuclear cells from patients with sepsis and mortality in septic mice model. Our findings uncover a novel mechanism by which the interaction between STING and NCOA4 regulates innate immune response and ferroptosis, which can be reversed by HET0016, providing mechanistic and promising targets insights into sepsis.
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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.