Fig. 5.

Mitochondrial mediated immune functions and cell signaling. Mitochondria can release molecules such as N-formyl peptides, mtDNA, ROS, and cardiolipin that initiate an immune response and related signaling pathways. N-formyl peptides are released and act as chemoattractants for neutrophils, binding to the FPR-1 receptor and promoting their activation and release of pro-inflammatory cytokines including TNFα, IL-1β, and IFNγ. MtDNA fragments (e.g. when the mtDNA is damaged by ROS) released from the organelle can also bind TLR9 receptors on neutrophils and likewise initiate the NF-κB pathway and release of TNFα and additional cytokines. Mitochondrial anti-viral signaling (MAVS) located on the outer membrane can be activated by viral RNA and/or. ROS, also triggering activation of the NF-κB pathway and the release of interferon regulating factors (IRFs). Additionally, MAVS can promote the oligomerization and activation of the NLRP3 inflammasome which triggers Caspase-1 cell death pathways and the activation of the pro-inflammatory forms of IL-1β and IL-18. In addition to being activated by MAVS, NLRP3 can also be activated by ROS, mtDNA, and cardiolipin.