ArticleThe Journal of clinical investigation2022
Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 18 citations in OpenAlex.
- Identification and characterization of tryptophan metabolism-related genes in carotid artery plaques.PloS one · 2026Article
- How Effectively Can Oxidative Stress and Inflammation Be Reversed When CFTR Function Is Pharmacologically Improved?Antioxidants (Basel, Switzerland) · 2025Review
- Cellular senescence in Alzheimer's disease: from physiology to pathology.Translational neurodegeneration · 2024Review
- IL-1 receptor antagonism reveals a yin-yang relationship between NFκB and interferon signaling in chronic lymphocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The circadian control of tryptophan metabolism regulates the host response to pulmonary fungal infections.PNAS nexus · 2023Article
- Turning Microbial AhR Agonists into Therapeutic Agents via Drug Delivery Systems.Pharmaceutics · 2023Review
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
30 authors at 4 institutions in 3 countries.
Funding
Abstract
Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here, we define a molecular pathway through which recombinant IL-1 receptor antagonist (IL-1Ra, anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynurenine pathway, transcriptionally activated NADPH oxidase 4 independent of the IL-1R1. By coupling the mitochondrial redox balance to autophagy, anakinra improved the dysregulated proteostasis network in murine and human cystic fibrosis. We anticipate that anakinra may represent a therapeutic option in addition to its IL-1R1-dependent antiinflammatory properties by acting at the intersection of mitochondrial oxidative stress and autophagy with the capacity to restore conditions in which defective proteostasis leads to human disease.
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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.