Mitochondria: Metabolic regulators of innate immune responses to pathogens and cell stress

Higher vertebrates have developed protective mechanisms that can detect stress-induced agents expressed during infection, stress or cellular damage. Innate sensing of these agents by Pattern Recognition Receptors enables downstream adaptive immunity to be primed, thereby mediating the body's appropriate response. Mitochondria, known as the cell powerhouse, have recently emerged as crucial regulators of the innate immune response to both pathogen infections and cell stress in various cell types unrestricted to immune cells. These highly dynamic organelles host numerous innate immune signaling modulators, of which some are directly linked to oxidative phosphorylation capacity and its control of oxidative stress. Therefore, mitochondrial bioenergetics is tightly connected to innate immunity and the extent of the immune response. In this short review, we shed light on how this bacteria “within” orchestrates innate immune responses at different levels by promoting a cellular metabolic reprogramming necessary to enhance energy synthesis, and the release of host danger signals to alert subsequent cytosolic immune signaling cascades.