ArticleImmunity2015
Endoplasmic Reticulum Stress Activates the Inflammasome via NLRP3- and Caspase-2-Driven Mitochondrial Damage.
Article in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
252 citing papers in PubMed, 1 synthesis or guideline pooled it, 430 citations in OpenAlex.
- The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review.Cell communication and signaling : CCS · 2025Pooled it
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- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Stage-associated differences in injury and stress responses of hiPSC-derived cardiomyocytes under macrophage-derived inflammatory stimulation.Translational pediatrics · 2026Article
- Zinc accumulation in macrophages exacerbates metabolic dysfunction-associated steatotic liver disease progression.Signal transduction and targeted therapy · 2026Article
- CT1812 Attenuates Surgery-Induced Cognitive Impairment and Modulates TMEM97- and PGRMC1-Associated Hippocampal Stress Responses in Aged Mice.Neurochemical research · 2026Article
- Myeloid Cell-Specific Deletion of LGR4 Suppresses Atherosclerotic Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.Oncogene · 2026Article
- Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs.PLoS pathogens · 2026Article
- Death-associated protein kinase 2 (DAPK2) propagates endoplasmic reticulum stress in macrophages to worsen sepsis through HSPA5-IRE1α axis.Molecular biomedicine · 2026Article
- LPS-Induced Neuroinflammation in Neurodegenerative Diseases: A Double-Edged Sword?Molecular neurobiology · 2026Review
- Maresin 1 activates autophagy through SIRT1/PPAR-γ signaling to mitigate high glucose-induced pyroptosis in human retinal pigment epithelial cells.Experimental and therapeutic medicine · 2026Article
- SPHK1 deficiency promotes intestinal homeostasis by ameliorating ER stress-induced gastrointestinal injury during murine graft-versus-host disease.Science China. Life sciences · 2026Article
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exercise reverses high-fat diet-induced perivascular adipose tissue dysfunction through modulation of UCP2 and TXNIP/NLRP3 pathways.Journal of physiology and biochemistry · 2026Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Article
- Caspase-2 inhibits mitochondrial respiration in colorectal adenocarcinoma cells.Cell communication and signaling : CCS · 2026Article
192 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress is observed in many human diseases, often associated with inflammation. ER stress can trigger inflammation through nucleotide-binding domain and leucine-rich repeat containing (NLRP3) inflammasome, which might stimulate inflammasome formation by association with damaged mitochondria. How ER stress triggers mitochondrial dysfunction and inflammasome activation is ill defined. Here we have used an infection model to show that the IRE1α ER stress sensor regulates regulated mitochondrial dysfunction through an NLRP3-mediated feed-forward loop, independently of ASC. IRE1α activation increased mitochondrial reactive oxygen species, promoting NLRP3 association with mitochondria. NLRP3 was required for ER stress-induced cleavage of caspase-2 and the pro-apoptotic factor, Bid, leading to subsequent release of mitochondrial contents. Caspase-2 and Bid were necessary for activation of the canonical inflammasome by infection-associated or general ER stress. These data identify an NLRP3-caspase-2-dependent mechanism that relays ER stress to the mitochondria to promote inflammation, integrating cellular stress and innate immunity.
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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.