Mitochondria are the powerhouses of immunity

Abstract

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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Figure 1: Mitochondria as a signaling hub.
Figure 2: Mitochondrial dynamics regulate immune-cell function.
Figure 3: Succinate as a proinflammatory signal acting via SDH and RET in complex I.
Figure 4: Citrate and itaconate are key regulators of inflammation and antibacterial host defense.
Figure 5: FAO is required for Tm cell, Treg cell, M2 macrophage and antiviral DC responses.
Figure 6: The aspartate–arginosuccinate shunt and macrophage activation.

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This work was supported by grants from Science Foundation Ireland and The Wellcome Trust.

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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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