IMR Press / FBL / Volume 22 / Issue 6 / DOI: 10.2741/4530

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Clinical implications and pathological associations of circulating mitochondrial DNA

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1 Department of Traumatology, John Hunter Hospital, Lookout Road, New Lambton Height, NSW 2305 Newcastle, NSW 2310, Australia
2 Department of Traumatology, University of Newcastle, University Drive, Callaghan NSW 2308, Australia

Academic Editor: Mikhail F Alexeyev

Front. Biosci. (Landmark Ed) 2017, 22(6), 1011–1022; https://doi.org/10.2741/4530
Published: 1 January 2017
(This article belongs to the Special Issue Mitochondrial DNA)
Abstract

Mitochondria are membrane-enclosed organelles, the energy-producing centers in almost all eukaryotic cells. The evolutionary emergence of mitochondria is a result of the endocytosis of a-proteobacteria. There are several characteristic features which refer to its prokaryotic ancestors including its independent sets of double-stranded mitochondrial DNA, which is uniquely circular in form and contains a significant amount of unmethylated DNA as CpG islands. Resent research has proven that free mitochondrial DNA found in blood was associated with innate immunomodulation in a broad-range of clinical conditions. Upon release, mitochondrial DNA acts as a danger-associated molecular pattern in the circulation, it is recognized by pattern recognition receptors and it facilitates inflammatory responses. Besides its high receptor activation potential, mitochondrial DNA is likely to perform direct crosstalk with activated leukocytes and to be contributed to other anti-microbial activities. Here we highlight the pathological conditions where cell free mtDNA is involved, describe the potential sources and mechanisms of extracellular mtDNA release and explore evidence for its mechanism of action after being excreted and potential therapeutic strategies.

Keywords
Mitochondria
Mitochondrial DNA
mtDNA
Inflammation
Organ Failure
Review
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