Powerhouses of lethality: mitochondria in macrophage antimicrobial activity

Macrophages employ multiple strategies to dispatch phagocytosed microbes, including bombardment with toxic compounds and radicals, or the deprivation of key nutrients. The lethality of macrophages depends on their ability to regulate levels of microbicidal effectors and proper targeting of these effectors to the phagosome, where many intracellular pathogens are detained. Mitochondria play important roles in establishing an antimicrobial phagosomal environment in macrophages, playing roles in both the production and targeting of these effectors. In response to infection, the mitochondrial network undergoes dramatic structural and functional perturbations that modulate macrophage microbicidal potential. As central coordinators of cellular metabolism, mitochondria control the abundance of metabolites that can either be toxic to ingested microbes or necessary for their growth. Mitochondria are also prolific producers of reactive oxygen species (ROS), which play direct roles in killing microbes and serve as signaling molecules to coordinate antimicrobial responses. While mitochondria are also known to play extensive roles in regulating cytokine production and proinflammatory responses, this review will focus on highlighting mechanisms by which mitochondria manipulate the macrophage microbicidal milieu.