Fig. 3.

The role of mtDNA in activating the innate immune response. Ischaemic damage-induced loss of membrane potential and mitochondrial swelling can lead to opening of a non-selective permeability transition pore (MPTP) in the mitochondrial inner membrane that releases mitochondrial molecules, like cytochrome c, ATP, ROS, N-formyl peptides and mtDNA, into the cytosol. Released mitochondrial components can act as mitochondrial damage associated molecular patterns (mtDAMPs). When released, they function as signals for injury in cells and activate the innate immune response. MtDNA, due to its similarity to bacterial DNA, can activate the TLR9 dependent immune response and in turn stimulate activation of the transcription factor NF-κB and therefore expression of the cytokine IL-6, which is released from the cell and functions as a stimulus for immune cells. In addition, mtDNA is involved in the activation of the NLRP3 inflammasome that senses cytosolic DNA and stimulates the caspase-1-dependent release of IL-1β and IL-18. Furthermore, the ER-linked STING pathway can be activated inducing the expression of interferon type 1 and its inflammatory signalling pathways