ArticleThe EMBO journal2023
MARCH5-dependent NLRP3 ubiquitination is required for mitochondrial NLRP3-NEK7 complex formation and NLRP3 inflammasome activation.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 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
- Mitochondria: a breakthrough in combating rheumatoid arthritis.Frontiers in medicine · 2024Pooled it
- Review
- Reprogramming of the hepatic ubiquitin‑immune axis: A unifying mechanism in liver disease progression (Review).Molecular medicine reports · 2026Review
- Advances in the Core Role and Mechanisms of Mitochondrial Dysfunction in Alzheimer's Disease.Brain and behavior · 2026Review
- The Mechanism of NLRP3 Inflammasome Activation and Its Roles in Chronic Rhinosinusitis.World journal of otorhinolaryngology - head and neck surgery · 2026Review
- Mitochondrial Regulation of the NLRP3 Inflammasome in Diabetic Kidney Disease: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2026Review
- USP13 ameliorates diabetic cardiomyopathy via deubiquitinating NLRP3 and inhibiting pyroptosis in cardiomyocytes.Cell death and differentiation · 2026Article
- The NLRP3 Inflammasome in Neuropsychiatric Disorders: Molecular Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Diverse Scaffolds Facilitate NLRP3 Clustering and Inflammasome Formation in Response to Perturbations in Cell Homeostasis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- Mitochondria and polycystic ovary syndrome: The role of ferroptosis, inflammasomes, and endoplasmic reticulum stress.International journal of biological sciences · 2026Review
- SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury.Research (Washington, D.C.) · 2026Article
- Deciphering the NEK7-NLRP3 inflammasome assembly: from conformational activation to allosteric drug discovery.Frontiers in immunology · 2026Review
- NEK7 couples SDHB to orchestrate respiratory chain electron transport homeostasis that impedes liver fibrosis.Nature communications · 2025Article
- Optineurin is an adaptor protein for ubiquitinated substrates in Golgi membrane-associated degradation.Nature communications · 2025Article
- The E3 ubiquitin ligase MARCH9 alleviates pyroptosis by regulating NLPR3 ubiquitination following myocardial ischemia reperfusion.Cellular and molecular life sciences : CMLS · 2025Article
- HROB Induces Lung Adenocarcinoma Progression via ZC3HC1-CCNB1 Axis Regulation and Cell Cycle Dysregulation.Cancer science · 2025Article
- CRL2BMC biology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NLRP3 inflammasome plays a key role in responding to pathogens, and endogenous damage and mitochondria are intensively involved in inflammasome activation. The NLRP3 inflammasome forms multiprotein complexes and its sequential assembly is important for its activation. Here, we show that NLRP3 is ubiquitinated by the mitochondria-associated E3 ligase, MARCH5. Myeloid cell-specific March5 conditional knockout (March5 cKO) mice failed to secrete IL-1β and IL-18 and exhibited an attenuated mortality rate upon LPS or Pseudomonas aeruginosa challenge. Macrophages derived from March5 cKO mice also did not produce IL-1β and IL-18 after microbial infection. Mechanistically, MARCH5 interacts with the NACHT domain of NLRP3 and promotes K27-linked polyubiquitination on K324 and K430 residues of NLRP3. Ubiquitination-defective NLRP3 mutants on K324 and K430 residues are not able to bind to NEK7, nor form NLRP3 oligomers leading to abortive ASC speck formation and diminished IL-1β production. Thus, MARCH5-dependent NLRP3 ubiquitination on the mitochondria is required for NLRP3-NEK7 complex formation and NLRP3 oligomerization. We propose that the E3 ligase MARCH5 is a regulator of NLRP3 inflammasome activation on the mitochondria.
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