Mitochondrial
            <scp>DNA</scp>
            in inflammation and immunity

Riley, Joel S.; Tait, Stephen W.G.

doi:10.15252/embr.201949799

Cited by 529 publications

(473 citation statements)

References 214 publications

(271 reference statements)

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“…4,6 In the normal physiological setting, mtDNA within cells is being constantly replicated and replaced via degradation during the mitochondrial life cycle and can act as a signalling molecule. 10 However, if the mitochondrial life cycle is disrupted and the degradation of damaged mtDNA is impaired, mtDNA can leak out of the mitochondria into the cytosol or the peripheral circulation. Due to its resemblance to bacterial genomes, this cell-free (cf) mtDNA can activate the TLR-9 pathway, leading to activation of TNF-alpha and a downstream inflammatory response.…”

mentioning

confidence: 99%

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

et al. 2020

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Circulating mitochondrial DNA (mtDNA), widely studied as a disease biomarker, comprises of mtDNA located within mitochondria, indicative of mitochondrial function, and cell‐free (cf) mtDNA linked to inflammation. The purpose of this study was to determine the ranges of, and relationship between, cellular and cf mtDNA in human blood. Whole blood from 23 controls (HC) and 20 patients with diabetes was separated into peripheral blood mononuclear cells (PBMCs), plasma, and serum. Total DNA was isolated and mtDNA copy numbers were determined using absolute quantification. Cellular mtDNA content in PBMCs was higher than in peripheral blood and a surprisingly high level of cf mtDNA was present in serum and plasma of HC, with no direct relationship between cellular and cf mtDNA content within individuals. Diabetes patients had similar levels of cellular mtDNA compared to healthy participants but a significantly higher cf mtDNA content. Furthermore, only in patients with diabetes, we observed a correlation between whole blood and plasma mtDNA levels, indicating that the relationship between cellular and cf mtDNA content is affected by disease status. In conclusion, when evaluating mtDNA in human blood as a biomarker of mitochondrial dysfunction, it is important to measure both cellular and cf mtDNA.

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confidence: 99%

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

et al. 2020

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“…Perhaps the differences (or lack thereof) in mitochondrial-gene expression are a byproduct of mitochondrial small open reading frame post-transcriptional regulation or the immune-signaling capacity of mitochondrial RNA and DNA released into the cytoplasm. [14][15][16] Second, we found that SARS-CoV-2 did not alter MAVS expression, whereas IAV, HPIV, and RSV all decreased MAVS expression. Although SARS-CoV-2 differentially regulates the host cell's interferon response, MAVS is not directly regulated by interferons.…”

Section: Discussionmentioning

confidence: 64%

SARS-CoV-2 induces a unique mitochondrial transcriptome signature

Miller

Silverstein

Flores

et al. 2020

Preprint

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SARS-CoV-2 has challenged global healthcare systems in part because its clinical manifestations are heterogeneous. Variable symptoms of SARS-CoV-2 could be attributed to the virus’ ability to mildly induce an innate immune response, as prior transcriptomic data has suggested. Mitochondrial dynamics might partially mediate the effect of SARS-CoV-2 on innate immunity. Many proteins encoded by SARS-CoV have been shown to localize to mitochondria and inhibit Mitochondrial Antiviral Signaling protein (MAVS). We analyzed multiple publicly available RNASeq data in order to unravel the metabolic and mitochondrial transcriptome signature of SARS-CoV-2 in primary cells, cell lines, and clinical samples (i.e., BALF and lung). We report here that SARS-CoV-2 does not dramatically regulate (1) mitochondrial-gene expression or (2) MAVS expression, but (3) downregulates nuclear-encoded mitochondrial (NEM) genes related to cellular respiration and Complex 1 assembly. We also report cell-specific and tissue-specific effects of SARS-CoV-2 on the mitochondrial-encoded and NEM transcriptome that could inform future experimental paradigm selection.

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“…For instance, the most prominent hit with pan-viral antiviral activity was IRF1, a transcription factor responsible for IFN-independent induction of some ISGs. The same screen also identified the DNA-sensor cGAS as a gene with broad antiviral function against DNA-, but also RNA viruses, which may partially be explained by virus-mediated secondary effects such as mitochondrial damage [ 58 , 59 ].…”

Section: Genetic Screensmentioning

confidence: 99%

System-Based Approaches to Delineate the Antiviral Innate Immune Landscape

Krey

Babnis

Pichlmair

2020

Viruses

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Viruses pose substantial challenges for society, economy, healthcare systems, and research. Their distinctive pathologies are based on specific interactions with cellular factors. In order to develop new antiviral treatments, it is of central importance to understand how viruses interact with their host and how infected cells react to the virus on a molecular level. Invading viruses are commonly sensed by components of the innate immune system, which is composed of a highly effective yet complex network of proteins that, in most cases, mediate efficient virus inhibition. Central to this process is the activity of interferons and other cytokines that coordinate the antiviral response. So far, numerous methods have been used to identify how viruses interact with cellular processes and revealed that the innate immune response is highly complex and involves interferon-stimulated genes and their binding partners as functional factors. Novel approaches and careful experimental design, combined with large-scale, high-throughput methods and cutting-edge analysis pipelines, have to be utilized to delineate the antiviral innate immune landscape at a global level. In this review, we describe different currently used screening approaches, how they contributed to our knowledge on virus–host interactions, and essential considerations that have to be taken into account when planning such experiments.

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Mitochondrial DNA in inflammation and immunity

Cited by 529 publications

References 214 publications

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

SARS-CoV-2 induces a unique mitochondrial transcriptome signature

System-Based Approaches to Delineate the Antiviral Innate Immune Landscape

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