Nitric Oxide Evokes an Adaptive Response to Oxidative Stress by Arresting Respiration

摘要: Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components electron transport chain (ETC). Basal levels oxidative stress can dramatically rise upon activation NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms express a battery low-molecular-weight thiol scavengers, legion detoxifying catalases, peroxidases, superoxide dismutases, as well variety repair systems. We present herein blockage bacterial respiration novel strategy that helps intracellular pathogen Salmonella survive extreme conditions. A strain bearing mutations in complex I NADH dehydrogenases is refractory to early antimicrobial activity IFNγ-activated macrophages. The ability NADH-rich, I-deficient associated with resistance peroxynitrite (ONOO-) hydrogen peroxide (H2O2). Inhibition nitric oxide (NO) also triggered protective adaptive response against stress. Expression NDH-II dehydrogenase decreases levels, thereby abrogating NO-adapted H2O2. antagonizes hydroxyl radical (OH·) generated classical Fenton chemistry or spontaneous decomposition peroxynitrous acid (ONOOH), while fueling AhpCF alkylhydroperoxidase. Together, these findings identify accumulation following NO-mediated inhibition Salmonella's ETC antioxidant strategy. NO-dependent arrest may help mitochondria plethora cope engendered situations diverse aerobic respiration, ischemia reperfusion, inflammation.