ArticleNature communications2021
The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 76 citations in OpenAlex.
- Mitophagy in pathogenesis and therapeutic implications for infection.Experimental & molecular medicine · 2026Review
- From mitochondria to innate immunity: The mtDNA-driven cGAS/STING-NLRP3 cascade and its therapeutic implications in neurodegenerative diseases (Review).Experimental and therapeutic medicine · 2026Review
- Dilating the aging clock with light.Innovation (Cambridge (Mass.)) · 2026Review
- Advances in the Core Role and Mechanisms of Mitochondrial Dysfunction in Alzheimer's Disease.Brain and behavior · 2026Review
- Endosomes as central hubs of interorganellar communication and cellular homeostasis.Protein & cell · 2026Review
- Mitochondria as convergence hubs for innate immunity pathways.Communications biology · 2026Review
- Animal models accurately representing acute liver failure (Review).International journal of molecular medicine · 2026Review
- Plant natural products targeting NLRP3 inflammasome in Parkinson's disease: Molecular activation and regulation to therapeutics.iScience · 2026Review
- Enhancing Mitophagy with PEP-1-CAT Attenuates Vascular Inflammation and Atherogenesis in Mice.Inflammation · 2026Article
- Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity.Science (New York, N.Y.) · 2026Article
- Targeted regulation of adipose tissue macrophages from an immunometabolic perspective: a novel therapeutic approach for obesity-related metabolic disorders.Frontiers in immunology · 2026Review
- Mitophagy-pyroptosis-macrophage polarization crosstalk in cardiovascular diseases: mechanistic insights and therapeutic potential.Frontiers in cardiovascular medicine · 2026Review
- Engineering Tfh-Specific Nanoadjuvant to Counteract Bile Acid-Induced Mitophagy and Vaccine Hyporesponsivenes.Theranostics · 2026Article
- Research advances on NLRP3 inflammasomes in organ transplantation.Frontiers in immunology · 2026Review
- Gipc3 Mutation Might Cause Sensorineural Hearing Loss by Inhibiting Mitophagy in Inner Ear Hair Cells.Molecular neurobiology · 2025Article
- Adipocyte FMO3-derived TMAO induces WAT dysfunction and metabolic disorders by promoting inflammasome activation in ageing.Nature communications · 2025Article
- Single-cell transcriptome atlas reveals mitophagy dynamics in acute chemical injury model and the role of MSCs transplantation.Stem cell research & therapy · 2025Article
- Identification of mitophagy-related genes in patients with acute myocardial infarction.Hereditas · 2025Article
- Genetically Diverse Mycobacterium tuberculosis Isolates Manipulate Inflammasome and Interleukin 1β Secretion Independently of Macrophage Metabolic Rewiring.The Journal of infectious diseases · 2025Article
- TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways.Science advances · 2025Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although mitophagy is known to restrict NLRP3 inflammasome activation, the underlying regulatory mechanism remains poorly characterized. Here we describe a type of early endosome-dependent mitophagy that limits NLRP3 inflammasome activation. Deletion of the endosomal adaptor protein APPL1 impairs mitophagy, leading to accumulation of damaged mitochondria producing reactive oxygen species (ROS) and oxidized cytosolic mitochondrial DNA, which in turn trigger NLRP3 inflammasome overactivation in macrophages. NLRP3 agonist causes APPL1 to translocate from early endosomes to mitochondria, where it interacts with Rab5 to facilitate endosomal-mediated mitophagy. Mice deficient for APPL1 specifically in hematopoietic cell are more sensitive to endotoxin-induced sepsis, obesity-induced inflammation and glucose dysregulation. These are associated with increased expression of systemic interleukin-1β, a major product of NLRP3 inflammasome activation. Our findings indicate that the early endosomal machinery is essential to repress NLRP3 inflammasome hyperactivation by promoting mitophagy in macrophages.
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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 Socratic graph.