ArticleProceedings of the National Academy of Sciences of the United States of America2021
Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling.Biomolecules · 2026Review
- Mitochondrial Dysfunction in Ulcerative Colitis: Pathogenic Mechanisms and Novel Therapeutics.Journal of biochemical and molecular toxicology · 2026Review
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- Fat-targeted small molecule alleviates abnormal adipose tissue remodeling in obesity via SIRT3-driven mitophagy and inflammasome inhibition.Chinese medicine · 2025Article
- Intracellular IL1α in Peritumoral Monocytes Induces IL8 Production and Inhibits Mitophagy to Promote Stemness and Metastasis of Hepatocellular Carcinoma.Cancer research · 2025Article
- The N-terminal domain of precursor IL-1α enhances IL-6 expression via an intracrine mechanism in oral squamous cell carcinoma.Molecular biology reports · 2025Article
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Pattern Recognition by NOD-Like Receptors.Advances in experimental medicine and biology · 2025Review
- Lipid metabolic dysregulation-induced neuroinflammation in the pathophysiology of major depressive disorder.Frontiers in immunology · 2025Review
- Regulation of the NLRP3 inflammasome by autophagy and mitophagy.Immunological reviews · 2025Review
- Cardiolipin's multifaceted role in immune response: a focus on interacting proteins.Frontiers in immunology · 2025Review
- Article
- Mitochondrial dysfunction in sepsis: mechanisms and therapeutic perspectives.Critical care (London, England) · 2024Review
- HAX-1 interferes in assembly of NLRP3-ASC to block microglial pyroptosis in cerebral I/R injury.Cell death discovery · 2024Article
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases.Nature reviews. Cardiology · 2024Review
- Porcine β-Defensin 114: Creating a Dichotomous Response to Inflammation.International journal of molecular sciences · 2024Article
- Targeting NLRP3 inflammasome for neurodegenerative disorders.Molecular psychiatry · 2023Review
- NLRP3 and cancer: Pathogenesis and therapeutic opportunities.Pharmacology & therapeutics · 2023Review
- The mitophagy pathway and its implications in human diseases.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
The balance between NLRP3 inflammasome activation and mitophagy is essential for homeostasis and cellular health, but this relationship remains poorly understood. Here we found that interleukin-1α (IL-1α)-deficient macrophages have reduced caspase-1 activity and diminished IL-1β release, concurrent with reduced mitochondrial damage, suggesting a role for IL-1α in regulating this balance. LPS priming of macrophages induced pro-IL-1α translocation to mitochondria, where it directly interacted with mitochondrial cardiolipin (CL). Computational modeling revealed a likely CL binding motif in pro-IL-1α, similar to that found in LC3b. Thus, binding of pro-IL-1α to CL in activated macrophages may interrupt CL-LC3b-dependent mitophagy, leading to enhanced Nlrp3 inflammasome activation and more robust IL-1β production. Mutation of pro-IL-1α residues predicted to be involved in CL binding resulted in reduced pro-IL-1α-CL interaction, a reduction in NLRP3 inflammasome activity, and increased mitophagy. These data identify a function for pro-IL-1α in regulating mitophagy and the potency of NLRP3 inflammasome activation.
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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.