نقش ROS میتوکندری در ایمنی آنتی باکتریال The role of mitochondrial ROS in antibacterial immunity

Introduction The main function of mitochondria is the production of ATP in the process of oxidative phosphorylation. The main byproduct that is formed in the course of electron transport in the respiratory chain is superoxide anion radical. Superoxide emerges as a result of one-electron reduction of molecular oxygen in various parts of the respiratory chain, including Complex I (NADH: ubiquinone oxidoreductase), Complex II (succinate dehydrogenase), Complex III (ubiquinol: cytochrome oxidoreductase), and mitochondrial matrix dehydrogenases [Grivennikova and Vinogradov, 2013]. Subsequently, the superoxide gives rise to various reactive oxygen species (ROS). Normally, only 1-2% of the oxygen consumed by the cells are used for ROS formation in mitochondria (mtROS) [Turrens, 2003, Inoue et al., 2003]. Until recently, it was believed that mtROS predominantly play a destructive role causing cell damage and accelerating aging [Harman, 2003]. These views are exemplified by the ideas that are expressed in the work of Huang and co-workers [1997]. It was established that mice with a knockout of cytosolic CuZn-dependent superoxide dismutase gene are viable, while mice with a nonfunctional mitochondrial Mn-dependent superoxide dismutase gene do not survive. Recently, it has been established that mtROS formation is mandatory for the functioning of virtually all organs and tissues, being involved in numerous metabolic pathways and in the regulation of signaling processes [Dan Dunn et al., 2015]. Importantly, mtROS are essential for the functioning of the immune system. However, their influence may be either positive or negative, depending on the quantity of the mtROS involved. From the immunological viewpoint, the positive effects of mtROS are primarily based on their activating influence on antimicrobial immunity, while their negative effects, caused by their excessive production, result in the induction of autoinflammatory [van der Burgh and Boes, 2015] and autoimmune processes [Lee et al., 2016; Lood et al., 2016]. The formation of mtROS plays an important role in the development of the antiviral immunity including the production of proinflammatory cytokines by immune system cells [Kim et al., 2015]. This review is concerned with the analysis of the mtROS role in terms of antibacterial innate immunity.