Inflammasome activation leads to Caspase-1–dependent mitochondrial damage and block of mitophagy

Significance Sensors of the innate immune system trigger the induction of inflammatory responses upon infection and cellular stress. One such sensor is the inflammasome pathway, which is best described for its role in the production of the inflammatory cytokines IL-1β and IL-18. Other effector functions of the inflammasome pathway remain less well defined, and here we show that activation of this pathway leads to induction of mitochondrial damage and dismantling of the organelle. We link such mitochondrial damage to another inflammasome-regulated process called pyroptosis, which is a proinflammatory form of cell death. In summary, we characterize the role of mitochondrial damage during activation of the inflammasome pathway, of relevance to host defense and other physiological and pathophysiological settings.