ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Loss of Mitochondrial Protease CLPP Activates Type I IFN Responses through the Mitochondrial DNA-cGAS-STING Signaling Axis.
Article in Journal of immunology (Baltimore, Md. : 1950), 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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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.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- CLPP loss confers sex-specific protection from renal ischemia reperfusion injury.Redox biology · 2026Article
- Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease.Disease models & mechanisms · 2026Review
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Mitochondrial drivers of stem cell aging and inflammaging.npj aging · 2026Review
- Targeting VDAC1 to protect against mitochondria-linked cell death pathways: apoptosis, pyroptosis, ferroptosis, and associated diseases.Apoptosis : an international journal on programmed cell death · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Sterile inflammation in LHON: mitochondrial stress, innate immune signaling, and implications for AAV gene therapy.Frontiers in immunology · 2026Review
- Article
- 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction.Nature metabolism · 2025Article
- Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease.Nature communications · 2025Article
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects.Journal for immunotherapy of cancer · 2025Article
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Chemical activation of mitochondrial ClpP to modulate energy metabolism of CD4Cell reports. Medicine · 2024Article
- Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.Communications biology · 2024Article
- Review
- Mitochondrial DNA release and sensing in innate immune responses.Human molecular genetics · 2024Review
- Regulation of proteostasis and innate immunity via mitochondria-nuclear communication.The Journal of cell biology · 2024Review
- CLPP-Null Eukaryotes with Excess Heme Biosynthesis Show Reduced L-arginine Levels, Probably via CLPX-Mediated OAT Activation.Biomolecules · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a serine protease that degrades damaged or misfolded mitochondrial proteins. CLPP-null mice exhibit growth retardation, deafness, and sterility, resembling human Perrault syndrome, but also display immune system alterations. However, the molecular mechanisms and signaling pathways underlying immunological changes in CLPP-null mice remain unclear. In this study, we report the steady-state activation of type I IFN signaling and antiviral gene expression in CLPP-deficient cells and tissues, resulting in marked resistance to RNA and DNA virus infection. Depletion of the cyclic GMP-AMP (cGAS)-stimulator of IFN genes (STING) DNA sensing pathway reduces steady-state IFN-I signaling and abrogates the broad antiviral phenotype of CLPP-null cells. Moreover, we report that CLPP deficiency leads to mitochondrial DNA (mtDNA) instability and packaging alterations. Pharmacological and genetic approaches to deplete mtDNA or inhibit cytosolic release markedly reduce antiviral gene expression, implicating mtDNA stress as the driver of IFN-I signaling in CLPP-null mice. Our work places the cGAS-STING-IFN-I innate immune pathway downstream of CLPP and may have implications for understanding Perrault syndrome and other human diseases involving CLPP dysregulation.
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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.