Roles of Mitochondrial Sensing and Stress Response in the Regulation of Inflammation

Abstract

Mitochondria play critical roles in a wide variety of cellular functions beyond their intrinsic role as the energy powerhouse of the cell. Accumulating evidence has shown that mitochondria are deeply involved in innate immune responses to a variety of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Mitochondria serve as a signalling platform for antiviral innate immunity and are involved in the regulationof theNLRP3 inflammasome, an intracellular signalling complex required for the secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18. These findings suggest that mitochondrial conditions and integrity profoundly influence the extent and duration of inflammation. However, exposure of cells to various cytotoxic stressors easily causes damage to mitochondria and destroys mitochondrial integrity. If the damage is not severe, mitochondrial functions are maintained depending on the mitochondrial quality control system; however, once the damage exceeds capacity, cell-death– inducing signals are elicited by the mitochondria. Thus, mitochondrial sensing and stress response, aswell asmitochondrial quality control,may be critically involved not only in the overall cellular response but also in the regulation of inflammation. Keywords