Immunostimulatory role of mitochondrial DAMPs: alarming for pre-eclampsia?

Mitochondria are critical signaling organelles that play an integral cellular role in the activation of diverse physiological responses to perturbation. Mitochondrial damage-associated molecular patterns (DAMPs) act as redox signaling nodes synchronizing mitochondrial metabolism with triggering of inflammation. Oxidative stress and inflammation are implicated in the pathogenesis of pre-eclampsia; however, the mechanisms involved in the novel crosstalk between these two pathogenic pathways are less well elucidated. In this review, we show that mitochondrial redox signals are paramount for regulating and maintaining the inflammatory response to danger signals. Mitochondrial DNA (mtDNA) represents a mitochondrial DAMP and is often liberated as signal of mitochondrial dysfunction. This review will explore the mechanistic role of mitochondrial DNA in directly coordinating adaptive changes in the maternal inflammatory status in pre-eclampsia through recruitment of innate immune cells and subsequent cytokine production. Finally, we provide emerging evidence of elevated circulating mitochondrial DAMPs in pre-eclampsia.