The DOI matches its Crossref record; 121 of the 121 references it cites were found in a registry or an index.
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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In the citing paper
“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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Cites
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Circulating mitochondrial DAMPs cause inflammatory responses to injury
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Type I interferons in infectious disease
McNab, F., Mayer-Barber, K., Sher, A., Wack, A., & O'Garra, A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3787 · Cited by 2,780
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333
Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis
Shimada, K., Crother, T. R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V. K., Wolf, A. J., Vergnes, L., Ojcius, D. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.009 · Cited by 2,282
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975
Self-citationMitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803
Tlr signalling augments macrophage bactericidal activity through mitochondrial ros
West, A. P., Brodsky, I. E., Rahner, C., Woo, D. K., Erdjument-Bromage, H., Tempst, P., Walsh, M. C., Choi, Y., Shadel, G. S., & Ghosh, S. (2011) · Nature · doi:10.1038/nature09973 · Cited by 1,659
Self-citationLood, C., Blanco, L. P., Purmalek, M. M., Carmona-Rivera, C., De Ravin, S. S., Smith, C. K., Malech, H. L., Ledbetter, J. A., Elkon, K. B., & Kaplan, M. J. (2016) · Nature Medicine · doi:10.1038/nm.4027 · Cited by 1,570
Cited by
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Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Mitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813
Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins
Singh, R., Letai, A., & Sarosiek, K. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0089-8 · Cited by 2,111
Inflammation and immune dysfunction in Parkinson disease
Tansey, M. G., Wallings, R. L., Houser, M. C., Herrick, M. K., Keating, C. E., & Joers, V. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00684-6 · Cited by 1,382
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255
“Cytoplasmic DNA can originate from several sources, such as mtDNA released from stressed mitochondria 28 or cytoplasmic chromatin fragments (CCF) released from damaged nuclei 29,30 .”
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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