title: New tricks from an old dog: mitochondrial redox signaling in cellular inflammation.
abstract: Reactive oxygen species (ROS) such as superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) have long been implicated as pro-inflammatory, yet the sources of ROS and the molecular mechanisms by which they enhance inflammation have been less clear. Recent advances in the understanding of the molecular basis of inflammation mediated by the innate immune system have allowed these issues to be revisited. Although the Nox2 NADPH oxidases generate the bulk of ROS for antimicrobial host defense, recent studies have found that NADPH oxidase-dependent ROS production can actually dampen macrophage inflammatory responses to sterile pro-inflammatory stimuli. Instead, production of mitochondrial ROS has emerged as an important factor in both host defense and sterile inflammation. Excess mitochondrial ROS can be generated by either damage to the respiratory chain or by alterations of mitochondrial function such as those that increase membrane potential and reduce respiratory electron carriers. In autoinflammatory diseases, where key components of innate immune responses are activated by genetic mutations or environmental stimuli, inflammation has been found to be particularly sensitive to inhibition of mitochondrial ROS production. These findings have highlighted mitochondrial ROS as a novel generator of pro-inflammatory ROS and a potential therapeutic target in inflammatory diseases.
authors: Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors: Martin
authors: M
authors: Pelletier
authors: Talya S
authors: TS
authors: Lepow
authors: Leah K
authors: LK
authors: Billingham
authors: Michael P
authors: MP
authors: Murphy
authors: Richard M
authors: RM
authors: Siegel
mesh_terms: D002450:Cell Communication; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species
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