Clinical implications and pathological associations of circulating mitochondrial DNA.
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.
Department of Traumatology, John Hunter Hospital, Lookout Road, New Lambton Height, NSW 2305Newcastle, NSW 2310, Australia.
Eszter
E
Tuboly
Department of Traumatology, John Hunter Hospital, Lookout Road, New Lambton Height, NSW 2305 Newcastle, NSW 2310, Australia.
Daniel
D
Mcllroy
Department of Traumatology, University of Newcastle, University Drive, Callaghan NSW 2308, Australia.
Gabrielle
G
Briggs
Department of Traumatology, John Hunter Hospital, Lookout Road, New Lambton Height, NSW 2305 Newcastle, NSW 2310, Australia.
Natalie
N
Lott
Department of Traumatology, John Hunter Hospital, Lookout Road, New Lambton Height, NSW 2305 Newcastle, NSW 2310, Australia, zsolt.balogh@hnehealth.nsw.gov.au.
Zsolt J
ZJ
Balogh
D000818:Animals; D016923:Cell Death; D004272:DNA, Mitochondrial / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology; D009154:Mutation; D018384:Oxidative Stress; D013314:Stress, Mechanical
D004272:DNA, Mitochondrial