ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/006/SRR1688636/SRR1688636.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/004/SRR1688634/SRR1688634.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/007/SRR1688637/SRR1688637.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/000/SRR1688640/SRR1688640.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/009/SRR1688639/SRR1688639.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/008/SRR1688638/SRR1688638.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/001/SRR1688641/SRR1688641.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR168/005/SRR1688635/SRR1688635.fastq.gzprimaryOK200GenomicsFlavell Lab, Genetics/Immunobiology, Yale Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA269079Mus musculusxref:PubMed:25525875RNA sequencing of wild-type or Interferon Alpha receptor 1 Knockout MEF cells treated with DMSO or the Caspase Inhibitor Q-VD-OPh. The mechanism by which cells undergo death determines whether dying cells trigger inflammatory responses or remain immunologically silent. Mitochondria play a central role in the induction of cell death, as well as in immune signaling pathways. Here, we identify of a mechanism by which mitochondria and downstream pro-apoptotic caspases regulate the activation of antiviral immunity. In the absence of active caspases, mitochondrial outer membrane permeabilization by Bax and Bak results in the expression of type I interferons (IFNs). This induction is mediated by mitochondrial DNA-dependent activation of the cGAS/STING pathway and results in the establishment of a potent state of viral resistance. Our results show that mitochondria have the capacity to simultaneously expose a cell-intrinsic inducer of the IFN response, and to inactivate this response in a caspase-dependent manner. This mechanism provides a dual control, which determines whether mitochondria initiate an immunologically silent or a pro-inflammatory type of cell death. In order to determine whether the pharmacological inhibition of caspases could activate the type I interferon response, we treated WT MEFs with the caspase inhibitor Q-VD-OPH. The inhibitor induced an increased expression of ISGs, which was dependent on type I IFN receptor (IFNAR1) signaling. Overall design: RNA was extracted from duplicate samples and libraries generated for sequencing using the directional RNA-Seq library prep at the Yale Center for Genome Analysis. Libraries were sequenced using a Hiseq2500 sequencer to generate 76bp single-end reads. Duplicate samples were analyzed for each condition.ENADAGA4, mtDNA, DMDA, mitochondrial DNA, Caspase, DMDA1, mitochondrial genome, SCARMD2, Mitochondrial DNA., A4, MAM, SCG3, Interferon, TYPE, LGMD2CMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusApoptotic caspases prevent the induction of type I interferons by mitochondrial DNA2025-09-242014-12-04PRJNA269079GSE637941009025525875