Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases

Boyapati, Ray; Tamborska, Arina; Dorward, David A.; Ho, Gwo–Tzer

doi:10.12688/f1000research.10397.1

Cited by 138 publications

(116 citation statements)

References 137 publications

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“…Thus, the total amniotic fluid cell‐free nDNA in women with PPROM should be considered as a heterogeneous pool consisting of fetal tissue‐, placenta‐, maternal and fetal neutrophils‐, and bacteria‐derived cell‐free nDNA . The source of mtDNA is the mitochondria, which contain their own small circular genome that replicates independently of nDNA . In general, mtDNA are released by cells undergoing abnormal cell death …”

Section: Discussionmentioning

confidence: 99%

“…Currently, the assessment of cell‐free nDNA or mtDNA in different body fluids has gained attention in many areas of medicine . For example, in obstetrics, maternal blood cell‐free nDNA of fetal origin has been mainly used for noninvasive prenatal diagnosis .…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, its levels have been shown to be increased in various pregnancy complications such as miscarriage, preeclampsia, fetal growth restriction, and preterm delivery . In contrast to cell‐free nDNA, little is known about the relevance of cell‐free mtDNA in obstetrics; however, its blood levels were shown to be elevated in the presence of acute tissue injury, severe sepsis, systemic inflammatory response syndrome, and various types of cancer …”

Section: Introductionmentioning

confidence: 99%

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Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

et al. 2018

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Introduction We evaluated the levels of cell‐free nuclear DNA (nDNA) and cell‐free mitochondrial DNA (mtDNA) in the amniotic fluid supernatant from pregnancies complicated by preterm prelabor rupture of membranes (PPROM) based on evidence of microbial invasion of the amniotic cavity (MIAC) and/or intra‐amniotic inflammation (IAI). Material and methods A total of 155 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. The levels of cell‐free nDNA and mtDNA in the amniotic fluid supernatant were assessed and quantified by real‐time polymerase chain reaction. Results The levels of cell‐free nDNA and mtDNA were higher in women with MIAC and IAI than in women without these conditions (nDNA: with MIAC: median 3.9 × 104 genome equivalent [GE]/mL vs without MIAC: median 1.2 × 104 GE/mL, with IAI: median: 5.3 × 104 GE/mL vs without IAI: median 1.2 × 104 GE/mL; mtDNA: with MIAC: median 9.2 × 105 GE/mL vs without MIAC: median 2.5 × 105 GE/mL, with IAI: median 1.1 × 106 GE/mL vs without IAI: median 2.5 × 105; all P values ≤ 0.01). Women with the microbial‐associated IAI showed the highest levels of cell‐free nDNA and mtDNA. Conclusions Cell‐free nDNA and mtDNA are constituents of the amniotic fluid supernatant from PPROM pregnancies. Both cell‐free nDNA and mtDNA are involved in the intra‐amniotic inflammatory response in women with PPROM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

et al. 2018

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“…Of the known mitochondrial DAMPs, the one that has garnered the most interest is mtDNA (4, 11). There is a growing body of literature suggesting mtDNA is not only released in the setting of critical illness (12, 13), but can also propagate the inflammatory response through its interaction with the immune system (4, 5, 11).…”

Section: Introductionmentioning

confidence: 99%

“…There is a growing body of literature suggesting mtDNA is not only released in the setting of critical illness (12, 13), but can also propagate the inflammatory response through its interaction with the immune system (4, 5, 11). This is of particular interest as it raises the possibility that mtDNA may function as a surrogate of disease severity or even a predictor of mortality in critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA in Sepsis

Harrington

Choi

Nakahira

2017

Current Opinion in Critical Care

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Purpose of Review Our understanding of critical illness is transforming as we develop a better understanding of the impact pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) have on the pathogenesis of disease. Of the known DAMPs, there is a growing interest in mitochondrial DNA (mtDNA) as a DAMP capable of propagating the inflammatory response seen in sepsis and other conditions. In this review, we describe the varying mechanisms by which mtDNA is translocated from mitochondria into cytosol and the extracellular space where it can illicit an inflammatory response. Additionally, we present some of the most recent clinical studies to examine mtDNA in critical illness. Recent Findings Basic science research provides convincing data that mtDNA can influence the immune system through toll-like receptor 9 and inflammasomes. Clinical trials provide evidence that mtDNA is elevated in critically ill patients, and is associated with mortality. Summary While mtDNA is a DAMP shown to be elevated in numerous conditions the clinical ramifications of this finding remain elusive. Further work is needed to determine if mtDNA can be utilized as a biomarker of disease severity or mortality.

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New methods for analysing circulating cell‐free mitochondrial DNA

Hooten

2022

Clinical and Translational Dis

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Trauma, ischemia, inflammatory stress and environmental conditions can cause tissue injury and damage. This damage spurs the release of cellular components and debris into the extracellular environment, including damage associated molecular pattern (DAMP) molecules. These DAMPs are sensed by pattern recognition receptors that activate a cellular damage response to the pathological insult. Mitochondrial components have recently been recognised as potent DAMPs. 1,2 The mitochondrial genome shares features with bacterial genomes, due to their shared origin. Therefore, when mitochondrial DNA (mtDNA) is released into the extracellular space it is recognised as a foreign molecule and initiates an innate immune response. 1,2 Not only have DAMP molecules been of interest in studying the relationships between cellular damage and immune responses, but emerging evidence suggests that DAMPs may serve as 'liquid biopsies' to indicate tissue damage or disease status. For example, plasma levels of circulating cell-free mtDNA (ccf-mtDNA) can be isolated and quantified easily using quantitative real-time PCR (qPCR). The results of many studies suggest that there are higher levels of ccf-mtDNA after trauma, acute myocardial infarction, sepsis and in some inflammatory conditions. 3 A recent systematic review examined published articles on utilising ccf-mtDNA as a predictor of mortality in critically ill patients. 4 The authors noted that in their analysis there are inconsistencies in ccf-mtDNA isolation methods and quantification. For example, most often qPCRThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases

Cited by 138 publications

References 137 publications

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

Mitochondrial DNA in Sepsis

New methods for analysing circulating cell‐free mitochondrial DNA

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