biostudies-literatureNewman LENIA NIH HHSNCI NIH HHSNIAMS NIH HHSNIGMS NIH HHSNIH HHS194-206https://www.ebi.ac.uk/biostudies/studies/S-EPMC11026068biostudies-literatureUnknown26(2)Mitochondrial DNA (mtDNA) encodes essential subunits of the oxidative phosphorylation system, but is also a major damage-associated molecular pattern (DAMP) that engages innate immune sensors when released into the cytoplasm, outside of cells or into circulation. As a DAMP, mtDNA not only contributes to anti-viral resistance, but also causes pathogenic inflammation in many disease contexts. Cells experiencing mtDNA stress caused by depletion of the mtDNA-packaging protein, transcription factor A, mitochondrial (TFAM) or during herpes simplex virus-1 infection exhibit elongated mitochondria, enlargement of nucleoids (mtDNA-protein complexes) and activation of cGAS-STING innate immune signalling via mtDNA released into the cytoplasm. However, the relationship among aberrant mitochondria and Nature cell biologyMitochondrial DNA replication stress triggers a pro-inflammatory endosomal pathway of nucleoid disposal.PMC11026068T32 GM007198P30 AG068635P30 CA014195K99 GM141482F32 GM137580R00 CA245187R01 AR069876S10 OD023689Newman LETadepalle NShadel GSWeiser Novak STowers CGTremblay MELemersal IRojas GRGrotjahn DARodriguez-Enriquez RDonnelly MPGhosh SMedina MSchiavon CRChevez JAManor URocha SfalseMitochondrial DNA replication stress triggers a pro-inflammatory endosomal pathway of nucleoid disposal.Mitochondrial DNA (mtDNA) encodes essential subunits of the oxidative phosphorylation system, but is also a major damage-associated molecular pattern (DAMP) that engages innate immune sensors when released into the cytoplasm, outside of cells or into circulation. As a DAMP, mtDNA not only contributes to anti-viral resistance, but also causes pathogenic inflammation in many disease contexts. Cells experiencing mtDNA stress caused by depletion of the mtDNA-packaging protein, transcription factor A, mitochondrial (TFAM) or during herpes simplex virus-1 infection exhibit elongated mitochondria, enlargement of nucleoids (mtDNA-protein complexes) and activation of cGAS-STING innate immune signalling via mtDNA released into the cytoplasm. However, the relationship among aberrant mitochondria and 2024-01-01T00:00:00Z2024 Feb2025-04-04T01:36:02.09Z2025-04-04T01:36:02.09ZS-EPMC110260683833235310.1038/s41556-023-01343-1