{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T06:07:51Z","timestamp":1793858871424,"version":"4.6.1"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,3,14]]},"abstract":"<jats:p>Reactive oxygen species (ROS) have an established role in inflammation and host defense, as they kill intracellular bacteria and have been shown to activate the NLRP3 inflammasome. Here, we find that ROS generated by mitochondrial respiration are important for normal lipopolysaccharide (LPS)-driven production of several proinflammatory cytokines and for the enhanced responsiveness to LPS seen in cells from patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), an autoinflammatory disorder caused by missense mutations in the type 1 TNF receptor (TNFR1). We find elevated baseline ROS in both mouse embryonic fibroblasts and human immune cells harboring TRAPS-associated TNFR1 mutations. A variety of antioxidants dampen LPS-induced MAPK phosphorylation and inflammatory cytokine production. However, gp91phox and p22phox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits are dispensable for inflammatory cytokine production, indicating that NADPH oxidases are not the source of proinflammatory ROS. TNFR1 mutant cells exhibit altered mitochondrial function with enhanced oxidative capacity and mitochondrial ROS generation, and pharmacological blockade of mitochondrial ROS efficiently reduces inflammatory cytokine production after LPS stimulation in cells from TRAPS patients and healthy controls. These findings suggest that mitochondrial ROS may be a novel therapeutic target for TRAPS and other inflammatory diseases.<\/jats:p>","DOI":"10.1084\/jem.20102049","type":"journal-article","created":{"date-parts":[[2011,1,31]],"date-time":"2011-01-31T22:24:37Z","timestamp":1296512677000},"page":"519-533","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":792,"title":["Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS)"],"prefix":"10.1084","volume":"208","author":[{"given":"Ariel C.","family":"Bulua","sequence":"first","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"},{"name":"Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Simon","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikanth","family":"Maddipati","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kye-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Sack","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kastner","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Siegel","sequence":"additional","affiliation":[{"name":"Immunoregulation Section, Autoimmunity Branch 1 , and 2 , and 3"},{"name":"Inflammatory Biology Section, Laboratory of Clinical Investigation, National Institute of Arthritis and Musculoskeletal and Skin Diseases 1 , and 2 , and 3"},{"name":"Laboratory of Mitochondrial Biology in Cardiometabolic Syndromes, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1 , and 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2011,1,31]]},"reference":[{"key":"2023072522381239800_bib1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.cell.2005.02.001","article-title":"Mitochondria, oxidants, and aging","volume":"120","author":"Balaban","year":"2005","journal-title":"Cell."},{"key":"2023072522381239800_bib2","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.autrev.2008.04.006","article-title":"Autoimmune thyroiditis and ROS","volume":"7","author":"Burek","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"2023072522381239800_bib3","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1002\/eji.200636651","article-title":"Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-kappa B","volume":"37","author":"Bylund","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2023072522381239800_bib4","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/ni.1843","article-title":"HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species","volume":"11","author":"Capasso","year":"2010","journal-title":"Nat. Immunol."},{"key":"2023072522381239800_bib5","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.cell.2010.06.007","article-title":"Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria","volume":"142","author":"C\u00e1rdenas","year":"2010","journal-title":"Cell."},{"key":"2023072522381239800_bib6","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1152\/physrev.1979.59.3.527","article-title":"Hydroperoxide metabolism in mammalian organs","volume":"59","author":"Chance","year":"1979","journal-title":"Physiol. Rev."},{"key":"2023072522381239800_bib7","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1196\/annals.1447.045","article-title":"Role of increased ROS dissipation in prevention of T1D","volume":"1150","author":"Chen","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2023072522381239800_bib8","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.bbabio.2006.02.019","article-title":"Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress","volume":"1757","author":"Chernyak","year":"2006","journal-title":"Biochim. Biophys. Acta."},{"key":"2023072522381239800_bib9","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1073\/pnas.0510965103","article-title":"Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses","volume":"103","author":"Chi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072522381239800_bib10","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1007\/s00281-006-0015-6","article-title":"Hereditary auto-inflammatory disorders and biologics","volume":"27","author":"Church","year":"2006","journal-title":"Springer Semin. Immunopathol."},{"key":"2023072522381239800_bib11","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1074\/jbc.M608083200","article-title":"ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages","volume":"282","author":"Cruz","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2023072522381239800_bib12","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1126\/science.1156995","article-title":"Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica","volume":"320","author":"Dostert","year":"2008","journal-title":"Science."},{"key":"2023072522381239800_bib13","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1111\/j.1365-2249.2008.03634.x","article-title":"Redox signalling and the inflammatory response in rheumatoid arthritis","volume":"152","author":"Filippin","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"2023072522381239800_bib14","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1002\/eji.200737348","article-title":"Th17 development and autoimmune arthritis in the absence of reactive oxygen species","volume":"38","author":"George-Chandy","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2023072522381239800_bib15","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s00415-004-0348-9","article-title":"The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy","volume":"251","author":"Gilgun-Sherki","year":"2004","journal-title":"J. Neurol."},{"key":"2023072522381239800_bib16","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1056\/NEJMoa055137","article-title":"Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition","volume":"355","author":"Goldbach-Mansky","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2023072522381239800_bib17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1042\/bj2420103","article-title":"The inhibition by diphenyleneiodonium and its analogues of superoxide generation by macrophages","volume":"242","author":"Hancock","year":"1987","journal-title":"Biochem. J."},{"key":"2023072522381239800_bib18","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1016\/S0140-6736(04)17401-1","article-title":"Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist","volume":"364","author":"Hoffman","year":"2004","journal-title":"Lancet."},{"key":"2023072522381239800_bib19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1042\/bj1290039","article-title":"Biochemical effects of the hypoglycaemic compound diphenyleneiodonnium. Catalysis of anion-hydroxyl ion exchange across the inner membrane of rat liver mitochondria and effects on oxygen uptake","volume":"129","author":"Holland","year":"1972","journal-title":"Biochem. J."},{"key":"2023072522381239800_bib20","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1097\/00005792-200209000-00002","article-title":"The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder","volume":"81","author":"Hull","year":"2002","journal-title":"Medicine (Baltimore)."},{"key":"2023072522381239800_bib21","doi-asserted-by":"publisher","first-page":"12646","DOI":"10.1073\/pnas.0403831101","article-title":"Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene","volume":"101","author":"Hultqvist","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072522381239800_bib22","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.cell.2004.12.041","article-title":"Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases","volume":"120","author":"Kamata","year":"2005","journal-title":"Cell."},{"key":"2023072522381239800_bib23","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1189\/jlb.0407259","article-title":"Apoptosis triggered by phagocytosis-related oxidative stress through FLIPS down-regulation and JNK activation","volume":"82","author":"Kanayama","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"2023072522381239800_bib24","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nri1312","article-title":"NOX enzymes and the biology of reactive oxygen","volume":"4","author":"Lambeth","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"2023072522381239800_bib25","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1172\/JCI200314172","article-title":"Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension","volume":"111","author":"Landmesser","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2023072522381239800_bib26","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1006\/bbrc.1998.9729","article-title":"Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production","volume":"253","author":"Li","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023072522381239800_bib27","doi-asserted-by":"publisher","first-page":"8516","DOI":"10.1074\/jbc.M210432200","article-title":"Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production","volume":"278","author":"Li","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023072522381239800_bib28","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1182\/blood-2005-11-006783","article-title":"Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS)","volume":"108","author":"Lobito","year":"2006","journal-title":"Blood."},{"key":"2023072522381239800_bib29","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/ni.1857","article-title":"TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages","volume":"11","author":"Martinon","year":"2010","journal-title":"Nat. Immunol."},{"key":"2023072522381239800_bib30","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1182\/blood-2010-01-264218","article-title":"Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease","volume":"116","author":"Meissner","year":"2010","journal-title":"Blood."},{"key":"2023072522381239800_bib31","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S1097-2765(02)00445-8","article-title":"Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo","volume":"9","author":"Meng","year":"2002","journal-title":"Mol. Cell."},{"key":"2023072522381239800_bib32","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.freeradbiomed.2009.05.018","article-title":"Regulation of superoxide dismutase genes: implications in disease","volume":"47","author":"Miao","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"2023072522381239800_bib33","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1084\/jem.185.2.207","article-title":"Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus","volume":"185","author":"Morgenstern","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072522381239800_bib34","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1146\/annurev.pharmtox.47.120505.105110","article-title":"Targeting antioxidants to mitochondria by conjugation to lipophilic cations","volume":"47","author":"Murphy","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"2023072522381239800_bib35","first-page":"1176","article-title":"Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice","volume":"118","author":"Nakano","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2023072522381239800_bib36","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1172\/JCI200318174","article-title":"Specificity of a third kind: reactive oxygen and nitrogen intermediates in cell signaling","volume":"111","author":"Nathan","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2023072522381239800_bib37","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"2023072522381239800_bib38","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.biocel.2008.10.011","article-title":"The p53-p66shc-Manganese Superoxide Dismutase (MnSOD) network: a mitochondrial intrigue to generate reactive oxygen species","volume":"41","author":"Pani","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2023072522381239800_bib39","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1038\/sj.cdd.4402195","article-title":"Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration","volume":"14","author":"P\u00e9trilli","year":"2007","journal-title":"Cell Death Differ."},{"key":"2023072522381239800_bib40","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/ng0295-202","article-title":"Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production","volume":"9","author":"Pollock","year":"1995","journal-title":"Nat. Genet."},{"key":"2023072522381239800_bib41","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1136\/ard.2005.048611","article-title":"Clinical significance of P46L and R92Q substitutions in the tumour necrosis factor superfamily 1A gene","volume":"65","author":"Ravet","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"2023072522381239800_bib42","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1038\/ni1202-1129","article-title":"Hydrogen peroxide as second messenger in lymphocyte activation","volume":"3","author":"Reth","year":"2002","journal-title":"Nat. Immunol."},{"key":"2023072522381239800_bib43","doi-asserted-by":"publisher","first-page":"S67","DOI":"10.1007\/s10875-007-9160-5","article-title":"Inflammatory manifestations in chronic granulomatous disease (CGD)","volume":"28","author":"Rosenzweig","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"2023072522381239800_bib44","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.4049\/jimmunol.161.10.5681","article-title":"Inhibition of MAP kinase kinase prevents cytokine and prostaglandin E2 production in lipopolysaccharide-stimulated monocytes","volume":"161","author":"Scherle","year":"1998","journal-title":"J. Immunol."},{"key":"2023072522381239800_bib45","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/0014-5793(92)80910-9","article-title":"NO., CO and. OH. Endogenous soluble guanylyl cyclase-activating factors","volume":"307","author":"Schmidt","year":"1992","journal-title":"FEBS Lett."},{"key":"2023072522381239800_bib46","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1002\/j.1460-2075.1993.tb05978.x","article-title":"Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF","volume":"12","author":"Schulze-Osthoff","year":"1993","journal-title":"EMBO J."},{"key":"2023072522381239800_bib47","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1182\/blood.V83.9.2669.2669","article-title":"Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation","volume":"83","author":"Sellak","year":"1994","journal-title":"Blood."},{"key":"2023072522381239800_bib48","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.bbamcr.2007.12.011","article-title":"Ero1 and redox homeostasis in the endoplasmic reticulum","volume":"1783","author":"Sevier","year":"2008","journal-title":"Biochim. Biophys. Acta."},{"key":"2023072522381239800_bib49","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1074-7613(00)80004-7","article-title":"Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase","volume":"10","author":"Shiloh","year":"1999","journal-title":"Immunity."},{"key":"2023072522381239800_bib50","doi-asserted-by":"publisher","first-page":"9801","DOI":"10.1073\/pnas.0914118107","article-title":"Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome","volume":"107","author":"Simon","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072522381239800_bib51","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1096\/fasebj.5.1.1703974","article-title":"Inhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs","volume":"5","author":"Stuehr","year":"1991","journal-title":"FASEB J."},{"key":"2023072522381239800_bib52","doi-asserted-by":"publisher","first-page":"6313","DOI":"10.4049\/jimmunol.0803422","article-title":"Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content","volume":"183","author":"Tagen","year":"2009","journal-title":"J. Immunol."},{"key":"2023072522381239800_bib53","doi-asserted-by":"publisher","first-page":"24233","DOI":"10.1074\/jbc.M212389200","article-title":"Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase","volume":"278","author":"Takada","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2023072522381239800_bib54","doi-asserted-by":"publisher","first-page":"9789","DOI":"10.1073\/pnas.1000779107","article-title":"Altered redox state of monocytes from cryopyrin-associated periodic syndromes causes accelerated IL-1beta secretion","volume":"107","author":"Tassi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072522381239800_bib55","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.neuroscience.2006.11.040","article-title":"A rotenone-sensitive site and H2O2 are key components of hypoxia-sensing in neonatal rat adrenomedullary chromaffin cells","volume":"145","author":"Thompson","year":"2007","journal-title":"Neuroscience."},{"key":"2023072522381239800_bib56","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1365-2567.2004.01942.x","article-title":"Mutant forms of tumour necrosis factor receptor I that occur in TNF-receptor-associated periodic syndrome retain signalling functions but show abnormal behaviour","volume":"113","author":"Todd","year":"2004","journal-title":"Immunology."},{"key":"2023072522381239800_bib57","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/humu.20080","article-title":"Infevers: an evolving mutation database for auto-inflammatory syndromes","volume":"24","author":"Touitou","year":"2004","journal-title":"Hum. Mutat."},{"key":"2023072522381239800_bib58","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/S0002-9440(10)63509-2","article-title":"Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models","volume":"163","author":"van de Loo","year":"2003","journal-title":"Am. J. Pathol."},{"key":"2023072522381239800_bib59","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.1073\/pnas.0914795107","article-title":"Reactive oxygen species-independent activation of the IL-1beta inflammasome in cells from patients with chronic granulomatous disease","volume":"107","author":"van de Veerdonk","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072522381239800_bib60","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1517\/13543781003727495","article-title":"Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations","volume":"19","author":"Villalba","year":"2010","journal-title":"Expert Opin. Investig. Drugs."},{"key":"2023072522381239800_bib61","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/sj.embor.7400687","article-title":"Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK","volume":"7","author":"Yang","year":"2006","journal-title":"EMBO Rep."},{"key":"2023072522381239800_bib62","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1038\/nature08206","article-title":"Riboflavin kinase couples TNF receptor 1 to NADPH oxidase","volume":"460","author":"Yazdanpanah","year":"2009","journal-title":"Nature."},{"key":"2023072522381239800_bib63","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."},{"key":"2023072522381239800_bib64","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2010","journal-title":"Nature."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/208\/3\/519\/1740476\/jem_20102049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/208\/3\/519\/1740476\/jem_20102049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T18:39:09Z","timestamp":1690310349000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/208\/3\/519\/41053\/Mitochondrial-reactive-oxygen-species-promote"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,31]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,3,14]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20102049","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.10308956.11647054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.10308956.11118054","asserted-by":"object"}]},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2011,1,31]]}}}