ArticleFrontiers in immunology2023
Apilimod activates the NLRP3 inflammasome through lysosome-mediated mitochondrial damage.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026Review
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Organelles and cancer cell pyroptosis: overview and perspectives.Cell death & disease · 2025Review
- Mechanisms of NLRP3 inflammasome in chronic kidney disease and the effects of traditional Chinese medicines.Renal failure · 2025Review
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives.RSC medicinal chemistry · 2025Review
- Development of a Second-Generation,Journal of medicinal chemistry · 2025Article
- Neuronal constitutive endolysosomal perforations enable α-synuclein aggregation by internalized PFFs.The Journal of cell biology · 2025Article
- Review
- Regulation of the NLRP3 inflammasome by autophagy and mitophagy.Immunological reviews · 2025Review
- Revealing the dance of NLRP3: spatiotemporal patterns in inflammasome activation.Immunometabolism (Cobham, Surrey) · 2025Review
- Mitochondria: a key regulator of programmed cell death in OP.Frontiers in endocrinology · 2025Review
- VCP Inhibition Augments NLRP3 Inflammasome Activation.Inflammation · 2024Article
- The Novel Role of the NLRP3 Inflammasome in Mycotoxin-Induced Toxicological Mechanisms.Veterinary sciences · 2024Review
- Progress in the Correlation Between Inflammasome NLRP3 and Liver Fibrosis.Journal of clinical and translational hepatology · 2024Review
- Lysosomal TRPML1 triggers global CaFrontiers in physiology · 2024Article
- Lysosomal BK channels facilitate silica-induced inflammation in macrophages.Inhalation toxicology · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NLRP3 is an important innate immune sensor that responses to various signals and forms the inflammasome complex, leading to IL-1β secretion and pyroptosis. Lysosomal damage has been implicated in NLRP3 inflammasome activation in response to crystals or particulates, but the mechanism remains unclear. We developed the small molecule library screening and found that apilimod, a lysosomal disruptor, is a selective and potent NLRP3 agonist. Apilimod promotes the NLRP3 inflammasome activation, IL-1β secretion, and pyroptosis. Mechanismically, while the activation of NLRP3 by apilimod is independent of potassium efflux and directly binding, apilimod triggers mitochondrial damage and lysosomal dysfunction. Furthermore, we found that apilimod induces TRPML1-dependent calcium flux in lysosomes, leading to mitochondrial damage and the NLRP3 inflammasome activation. Thus, our results revealed the pro-inflammasome activity of apilimod and the mechanism of calcium-dependent lysosome-mediated NLRP3 inflammasome activation.
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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.