ArticleCell2014
Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 591 papers.
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Who cites it
591 citing papers in PubMed, 924 citations in OpenAlex.
- PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma.Oncoimmunology · 2026Article
- 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
- After delivery: How recipient cells shape the fate and function of transplanted mitochondria.Clinical and translational medicine · 2026Review
- Comparative insights into the apoptosome, inflammasomes and PIDDosome.Nature reviews. Immunology · 2026Review
- MLN4924 suppresses kidney renal clear cell carcinoma progression through coordinated inhibition of Cullin1 neddylation and PSMB10-associated NF-κB inflammatory signaling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- PARP7 inhibitors enhance the immunogenic effects of radiation in pancreatic cancer cells.Molecular therapy. Oncology · 2026Article
- Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- Caspase-3 cleaves CYLD to restrict interferon signaling during mitochondrial apoptosis.EMBO reports · 2026Article
- The NETs-cGAS-STING Axis in Ischemic Stroke: Linking Neutrophil-Microglia Crosstalk, Immunothrombosis, and Neuroinflammation.Molecular neurobiology · 2026Review
- CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis.Nature communications · 2026Article
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- Leveraging Mitochondria-Endoplasmic Reticulum Functional Interplay With an On-Demand Nanoparticle to Boost mtDNA-Based STING Immunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Mitochondrial Mediated Apoptosis Evaluation of Myristicin on Triple Negative Breast Cancer Model Via Bcl2/Bid Pathway.Cell biochemistry and function · 2026Article
- A peptide-based screen for cell death inhibitors identifies the cytoprotective compound CDL36.bioRxiv : the preprint server for biology · 2026Article
- Specific bile acids can elicit the type-I interferon response through the cGAS-STING pathway.Cell communication and signaling : CCS · 2026Article
- Cancer frenemy pathways: Inducing immunogenic cell death by exploiting apoptosis-interferon antagonism with oncolytic viruses.Molecular therapy. Oncology · 2026Article
- NOXA/MCL-1 axis determines cell-death decision between apoptosis and a GSDME-dependent cell death associated with production of inflammatory cytokines upon treatment of breast cancer cells with antimitotics.Cell death & disease · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity.The Journal of clinical investigation · 2026Article
531 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Activated caspases are a hallmark of apoptosis induced by the intrinsic pathway, but they are dispensable for cell death and the apoptotic clearance of cells in vivo. This has led to the suggestion that caspases are activated not just to kill but to prevent dying cells from triggering a host immune response. Here, we show that the caspase cascade suppresses type I interferon (IFN) production by cells undergoing Bak/Bax-mediated apoptosis. Bak and Bax trigger the release of mitochondrial DNA. This is recognized by the cGAS/STING-dependent DNA sensing pathway, which initiates IFN production. Activated caspases attenuate this response. Pharmacological caspase inhibition or genetic deletion of caspase-9, Apaf-1, or caspase-3/7 causes dying cells to secrete IFN-β. In vivo, this precipitates an elevation in IFN-β levels and consequent hematopoietic stem cell dysfunction, which is corrected by loss of Bak and Bax. Thus, the apoptotic caspase cascade functions to render mitochondrial apoptosis immunologically silent.
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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.