Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells. These discoveries are revealing mitochondrial targets that could potentially be exploited for therapeutic gain in inflammation and cancer.
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This work was supported by grants from Science Foundation Ireland and The Wellcome Trust.
The authors declare no competing financial interests.
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Mills, E., Kelly, B. & O'Neill, L. Mitochondria are the powerhouses of immunity. Nat Immunol 18, 488–498 (2017). https://doi.org/10.1038/ni.3704
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