Mitochondrial DNA (mtDNA) can initiate an innate immune response when mislocalized in a compartment other than the mitochondrial matrix. mtDNA plays significant roles in regulating mitochondrial dynamics as well as mitochondrial unfolded protein response (UPR). The mislocalized extra-mtDNA can elicit innate immune response via cGAS–STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway, inducing the expression of the interferon-stimulated genes (ISGs). Also, cytosolic damaged mtDNA is cleared up by various pathways which are responsible for participating in the activation of inflammatory responses. Four pathways of extra-mitochondrial mtDNA clearance are highlighted in this review — the inflammasome activation mechanism, neutrophil extracellular traps formation, recognition by Toll-like receptor 9 and transfer of mtDNA between cells packaged into extracellular vesicles. Anomalies in these pathways are associated with various diseases. We posit our review in the present pandemic situation and discuss how mtDNA elicits innate immune responses against different viruses and bacteria. This review gives a comprehensive picture of the role of extra-mitochondrial mtDNA in infectious diseases and speculates that research towards its understanding would help establish its therapeutic potential.
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Cover Image
Cover Image
The plasma membrane of lymphocytes is highly compartmentalized in so-called nanodomains or protein islands. Proteins such as Caveolin-1 (pink), tetraspanins (blue) or flotillins (violet) define these protein islands and thereby regulate the functioning of the immune system. In this issue (see pages 2387–2397), Schaffer and Minguet discuss the importance of these protein islands regarding lymphocyte activation and the development of immunopathologies. This cover artwork has been created by Susana Minguet.
Mitochondrial DNA in innate immune responses against infectious diseases
Palamou Das, Oishee Chakrabarti; Mitochondrial DNA in innate immune responses against infectious diseases. Biochem Soc Trans 18 December 2020; 48 (6): 2823–2838. doi: https://doi.org/10.1042/BST20200687
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