{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xian H"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NCI NIH HHS","NIAMS NIH HHS"],"pagination":["1370-1385.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9378606"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["55(8)"],"pubmed_abstract":["Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization. This occurred independently of mtDNA or reactive oxygen species, which induce Ox-mtDNA generation. Within mitochondria, Ox-mtDNA was either repaired by DNA glycosylase OGG1 or cleaved by the endonuclease FEN1 to 500-650 bp fragments that exited mitochondria via mPTP- and VDAC"],"journal":["Immunity"],"pubmed_title":["Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling."],"pmcid":["PMC9378606"],"funding_grant_id":["R00 DK100640","P30 AR073761","P30 CA014195","K99 DK100640","K01 AR077111","U54 CA260591","R25 AI147376","P30 CA023100","R37 AI043477","R01 AR069876","R01 AI043477"],"pubmed_authors":["Shadel GS","Onyuru J","Hoffman HM","Offenberger J","Watari K","Xian H","Sampath H","Sanchez-Lopez E","Ying W","Karin M"],"additional_accession":[]},"is_claimable":false,"name":"Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling.","description":"Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization. This occurred independently of mtDNA or reactive oxygen species, which induce Ox-mtDNA generation. Within mitochondria, Ox-mtDNA was either repaired by DNA glycosylase OGG1 or cleaved by the endonuclease FEN1 to 500-650 bp fragments that exited mitochondria via mPTP- and VDAC","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2026-05-28T02:15:58.229Z","creation":"2026-04-08T02:07:57.23Z"},"accession":"S-EPMC9378606","cross_references":{"pubmed":["35835107"],"doi":["10.1016/j.immuni.2022.06.007"]}}