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Mitochondrial DNA in innate immune responses and inflammatory pathology
Open accessAbstract
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.
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“The combination of replicating mtDNA and ROS would oxidize the mtDNA, which would be released to activate the innate immune system inflammasome and the Type I interferon pathway (West and Shadel, 2017; Zhong et al., 2018).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as West and Shadel, 2017
In the citing paper
“Such a homeostatic function not only reflects the elimination of useless or potentially dangerous cells, but also the ability of dying cells to expose or release molecules that alert the organism or colony about a potential threat. Such danger signals are commonly referred to as damage-associated molecular patterns (DAMPs) or alarmins [19–22].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [19]
In the citing paper
“One of the strongest alarmins released by stressed mitochondria is mtDNA, which has emerged as a strong activator of innate immunity, particularly of the interferon signalling pathway201.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [201]
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Metadata
- Authors
- West, A. P., & Shadel, G. S.
- Affiliations
- Texas A&M Health Science Center (US)
- Yale University (US)
- Corresponding author
- West, A. Phillip
- Shadel, Gerald S.
- Venue
- Nature Reviews Immunology
- Published
- 2017-04-10
- Volume
- 17
- Issue
- 6
- Pages
- 363-375
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC7289178
- OpenAlex
- W2606232917
- Cited by
- 1,115
- References
- 121
- Citations by year
- 2026: 171 · 2025: 157 · 2024: 147 · 2023: 113 · 2022: 134 · 2021: 147 · 2020: 88 · 2019: 79 · 2018: 62 · 2017: 17
- FWCI
- 6.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG047632)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- mitochondrial DNA, innate immunity, pattern recognition receptors, type I interferon, inflammation, cellular stress, antimicrobial response, mitochondrial disease, oxidative phosphorylation
- MeSH terms
- Alarmins, Animals, DNA, Mitochondrial, Humans, Immunity, Innate, Inflammation
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