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Mitochondrial DNA in innate immune responses and inflammatory pathology

2017; Nature Portfolio; Volume: 17; Issue: 6 Linguagem: Inglês

10.1038/nri.2017.21

1474-1741

A. Phillip West, Gerald S. Shadel,

Inflammasome and immune disorders

Mitochondrial DNA (mtDNA) can engage multiple pattern-recognition receptors to trigger pro-inflammatory and type I interferon responses. This Review provides an overview of how these responses are activated by summarizing the unique features of mtDNA and how it is exposed during cellular stress. Mitochondrial DNA (mtDNA) — which is well known for its role in oxidative phosphorylation and maternally inherited mitochondrial diseases — is increasingly recognized as an agonist of the innate immune system that influences antimicrobial responses and inflammatory pathology. On entering the cytoplasm, extracellular space or circulation, mtDNA can engage multiple pattern-recognition receptors in cell-type- and context-dependent manners to trigger pro-inflammatory and type I interferon responses. Here, we review the expanding research field of mtDNA in innate immune responses to highlight new mechanistic insights and discuss the physiological and pathological relevance of this exciting area of mitochondrial biology.