Skip to main content
SpringerLink
Log in

Regulation of reactive oxygen species generation in cell signaling

  • Minireview
  • Published:
Molecules and Cells

Abstract

Reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide (H2O2) are thought to be byproducts of aerobic respiration with damaging effects on DNA, protein, and lipid. A growing body of evidence indicates, however, that ROS are involved in the maintenance of redox homeostasis and various cellular signaling pathways. ROS are generated from diverse sources including mitochondrial respiratory chain, enzymatic activation of cytochrome p450, and NADPH oxidases further suggesting involvement in a complex array of cellular processes. This review summarizes the production and function of ROS. In particular, how cytosolic and membrane proteins regulate ROS generation for intracellular redox signaling will be detailed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abo, A., Pick, E., Hall, A., Totty, N., Teahan, C.G., and Segal, A.W. (1991). Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature 353, 668–670.

    Article  PubMed  CAS  Google Scholar 

  • Adler, V., Yin, Z., Tew, K.D., and Ronai, Z. (1999). Role of redox potential and reactive oxygen species in stress signaling. Oncogene 18, 6104–6111.

    Article  PubMed  CAS  Google Scholar 

  • Ago, T., Kuribayashi, F., Hiroaki, H., Takeya, R., Ito, T., Kohda, D., and Sumimoto, H. (2003). Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. Proc. Natl. Acad. Sci. USA 100, 4474–4479.

    Article  PubMed  CAS  Google Scholar 

  • Ahluwalia, J., Tinker, A., Clapp, L.H., Duchen, M.R., Abramov, A.Y., Pope, S., Nobles, M., and Segal, A.W. (2004). The large-conductance Ca2+-activated K+ channel is essential for innate immunity. Nature 427, 853–858.

    Article  PubMed  CAS  Google Scholar 

  • Amanullah, A., Azam, N., Balliet, A., Hollander, C., Hoffman, B., Fornace, A., and Liebermann, D. (2003). Cell signalling: cell survival and a Gadd45-factor deficiency. Nature 424, 741; discussion 742.

    Article  PubMed  CAS  Google Scholar 

  • Ambasta, R.K., Kumar, P., Griendling, K.K., Schmidt, H.H., Busse, R., and Brandes, R.P. (2004). Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. J. Biol. Chem. 279, 45935–45941.

    Article  PubMed  CAS  Google Scholar 

  • Ameziane-El-Hassani, R., Morand, S., Boucher, J.L., Frapart, Y.M., Apostolou, D., Agnandji, D., Gnidehou, S., Ohayon, R., Noel-Hudson, M.S., Francon, J., et al. (2005). Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity. J. Biol. Chem. 280, 30046–30054.

    Article  PubMed  CAS  Google Scholar 

  • Andreyev, A.Y., Kushnareva, Y.E., and Starkov, A.A. (2005). Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 70, 200–214.

    Article  CAS  Google Scholar 

  • Baccala, R., Hoebe, K., Kono, D.H., Beutler, B., and Theofilopoulos, A.N. (2007). TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nat. Med. 13, 543–551.

    Article  PubMed  CAS  Google Scholar 

  • Bae, Y.S., Lee, J.H., Choi, S.H., Kim, S., Almazan, F., Witztum, J.L., and Miller, Y.I. (2009). Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ. Res. 104, 210–218, 221p following 218.

    Article  PubMed  CAS  Google Scholar 

  • Bae, S.H., Sung, S.H., Cho, E.J., Lee, S.K., Lee, H.E., Woo, H.A., Yu, D.Y., Kil, I.S., and Rhee, S.G. (2010). Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver. Hepatology 53, 945–953.

    Article  CAS  Google Scholar 

  • Balkwill, F., and Coussens, L.M. (2004). Cancer: an inflammatory link. Nature 431, 405–406.

    Article  PubMed  CAS  Google Scholar 

  • Banfi, B., Molnar, G., Maturana, A., Steger, K., Hegedus, B., Demaurex, N., and Krause, K.H. (2001). A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J. Biol. Chem. 276, 37594–37601.

    Article  PubMed  CAS  Google Scholar 

  • Banfi, B., Tirone, F., Durussel, I., Knisz, J., Moskwa, P., Molnar, G.Z., Krause, K.H., and Cox, J.A. (2004). Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5). J. Biol. Chem. 279, 18583–18591.

    Article  PubMed  CAS  Google Scholar 

  • Beutler, B. (2009). Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. Immunol. Rev. 227, 248–263.

    Article  PubMed  CAS  Google Scholar 

  • Bialik, S., Cryns, V.L., Drincic, A., Miyata, S., Wollowick, A.L., Srinivasan, A., and Kitsis, R.N. (1999). The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes. Circ. Res. 85, 403–414.

    PubMed  CAS  Google Scholar 

  • Bongartz, T., Sutton, A.J., Sweeting, M.J., Buchan, I., Matteson, E.L., and Montori, V. (2006). Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295, 2275–2285.

    Article  PubMed  CAS  Google Scholar 

  • Borregaard, N., Heiple, J.M., Simons, E.R., and Clark, R.A. (1983). Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. J. Cell Biol. 97, 52–61.

    Article  PubMed  CAS  Google Scholar 

  • Brand, M.D. (2010). The sites and topology of mitochondrial superoxide production. Exp. Gerontol. 45, 466–472.

    Article  PubMed  CAS  Google Scholar 

  • Brar, S.S., Corbin, Z., Kennedy, T.P., Hemendinger, R., Thornton, L., Bommarius, B., Arnold, R.S., Whorton, A.R., Sturrock, A.B., Huecksteadt, T.P., et al. (2003). NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am. J. Physiol. Cell Physiol. 285, C353–369.

    PubMed  CAS  Google Scholar 

  • Bravo, J., Karathanassis, D., Pacold, C.M., Pacold, M.E., Ellson, C.D., Anderson, K.E., Butler, P.J., Lavenir, I., Perisic, O., Hawkins, P.T., et al. (2001). The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate. Mol. Cell 8, 829–839.

    Article  PubMed  CAS  Google Scholar 

  • Brunelle, J.K., Bell, E.L., Quesada, N.M., Vercauteren, K., Tiranti, V., Zeviani, M., Scarpulla, R.C., and Chandel, N.S. (2005). Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab. 1, 409–414.

    Article  PubMed  CAS  Google Scholar 

  • Burdon, R.H., and Rice-Evans, C. (1989). Free radicals and the regulation of mammalian cell proliferation. Free Radic. Res. Commun. 6, 345–358.

    Article  PubMed  CAS  Google Scholar 

  • Cano, C.E., Gommeaux, J., Pietri, S., Culcasi, M., Garcia, S., Seux, M., Barelier, S., Vasseur, S., Spoto, R.P., Pebusque, M.J., et al. (2009). Tumor protein 53-induced nuclear protein 1 is a major mediator of p53 antioxidant function. Cancer Res. 69, 219–226.

    Article  PubMed  CAS  Google Scholar 

  • Caporossi, D., Ciafre, S.A., Pittaluga, M., Savini, I., and Farace, M.G. (2003). Cellular responses to H(2)O(2) and bleomycininduced oxidative stress in L6C5 rat myoblasts. Free Radic. Biol. Med. 35, 1355–1364.

    Article  PubMed  CAS  Google Scholar 

  • Chance, B., Sies, H., and Boveris, A. (1979). Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59, 527–605.

    PubMed  CAS  Google Scholar 

  • Chandel, N.S., Maltepe, E., Goldwasser, E., Mathieu, C.E., Simon, M.C., and Schumacker, P.T. (1998). Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA 95, 11715–11720.

    Article  PubMed  CAS  Google Scholar 

  • Chandel, N.S., McClintock, D.S., Feliciano, C.E., Wood, T.M., Melendez, J.A., Rodriguez, A.M., and Schumacker, P.T. (2000). Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J. Biol. Chem. 275, 25130–25138.

    Article  PubMed  CAS  Google Scholar 

  • Chang, T.S., Cho, C.S., Park, S., Yu, S., Kang, S.W., and Rhee, S.G. (2004). Peroxiredoxin III, a mitochondrion-specific peroxidase, regulates apoptotic signaling by mitochondria. J. Biol. Chem. 279, 41975–41984.

    Article  PubMed  CAS  Google Scholar 

  • Charles, I., Khalyfa, A., Kumar, D.M., Krishnamoorthy, R.R., Roque, R.S., Cooper, N., and Agarwal, N. (2005). Serum deprivation induces apoptotic cell death of transformed rat retinal ganglion cells via mitochondrial signaling pathways. Invest. Ophthalmol. Vis. Sci. 46, 1330–1338.

    Article  PubMed  Google Scholar 

  • Chen, G., and Goeddel, D.V. (2002). TNF-R1 signaling: a beautiful pathway. Science 296, 1634–1635.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Q., Powell, D.W., Rane, M.J., Singh, S., Butt, W., Klein, J.B., and McLeish, K.R. (2003a). Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J. Immunol. 170, 5302–5308.

    PubMed  CAS  Google Scholar 

  • Chen, Q., Vazquez, E.J., Moghaddas, S., Hoppel, C.L., and Lesnefsky, E.J. (2003b). Production of reactive oxygen species by mitochondria: central role of complex III. J. Biol. Chem. 278, 36027–36031.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, G., Diebold, B.A., Hughes, Y., and Lambeth, J.D. (2006). Nox1-dependent reactive oxygen generation is regulated by Rac1. J. Biol. Chem. 281, 17718–17726.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, G., and Lambeth, J.D. (2004). NOXO1, regulation of lipid binding, localization, and activation of Nox1 by the Phox homology (PX) domain. J. Biol. Chem. 279, 4737–4742.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, G., Ritsick, D., and Lambeth, J.D. (2004). Nox3 regulation by NOXO1, p47phox, and p67phox. J. Biol. Chem. 279, 34250–34255.

    Article  PubMed  CAS  Google Scholar 

  • Chipuk, J.E., Kuwana, T., Bouchier-Hayes, L., Droin, N.M., Newmeyer, D.D., Schuler, M., and Green, D.R. (2004). Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303, 1010–1014.

    Article  PubMed  CAS  Google Scholar 

  • Chipuk, J.E., Bouchier-Hayes, L., Kuwana, T., Newmeyer, D.D., and Green, D.R. (2005). PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309, 1732–1735.

    Article  PubMed  CAS  Google Scholar 

  • Choi, H., Leto, T.L., Hunyady, L., Catt, K.J., Bae, Y.S., and Rhee, S.G. (2008). Mechanism of angiotensin II-induced superoxide production in cells reconstituted with angiotensin type 1 receptor and the components of NADPH oxidase. J. Biol. Chem. 283, 255–267.

    Article  PubMed  CAS  Google Scholar 

  • Chung, Y.M., Kim, J.S., and Yoo, Y.D. (2006). A novel protein, Romo1, induces ROS production in the mitochondria. Biochem. Biophys. Res. Commun. 347, 649–655.

    Article  PubMed  CAS  Google Scholar 

  • Chung, Y.M., Lee, S.B., Kim, H.J., Park, S.H., Kim, J.J., Chung, J.S., and Yoo, Y.D. (2008). Replicative senescence induced by Romo1-derived reactive oxygen species. J. Biol. Chem. 283, 33763–33771.

    Article  PubMed  CAS  Google Scholar 

  • Chung, J.S., Lee, S.B., Park, S.H., Kang, S.T., Na, A.R., Chang, T.S., Kim, H.J., and Yoo, Y.D. (2009). Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27(Kip1) expression. Free Radic. Res. 43, 729–737.

    Article  PubMed  CAS  Google Scholar 

  • Clark, R.A., Leidal, K.G., Pearson, D.W., and Nauseef, W.M. (1987). NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxidegenerating system. J. Biol. Chem. 262, 4065–4074.

    PubMed  CAS  Google Scholar 

  • Coon, M.J. (2005). Cytochrome P450: nature’s most versatile biological catalyst. Annu. Rev. Pharmacol. Toxicol. 45, 1–25.

    Article  PubMed  CAS  Google Scholar 

  • Corda, S., Laplace, C., Vicaut, E., and Duranteau, J. (2001). Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am. J. Respir. Cell Mol. Biol. 24, 762–768.

    PubMed  CAS  Google Scholar 

  • Danielson, P.B. (2002). The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr. Drug Metab. 3, 561–597.

    Article  PubMed  CAS  Google Scholar 

  • De Deken, X., Wang, D., Many, M.C., Costagliola, S., Libert, F., Vassart, G., Dumont, J.E., and Miot, F. (2000). Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J. Biol. Chem. 275, 23227–23233.

    Article  PubMed  Google Scholar 

  • de Gasparo, M., Catt, K.J., Inagami, T., Wright, J.W., and Unger, T. (2000). International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol. Rev. 52, 415–472.

    Google Scholar 

  • de Mendez, I., Homayounpour, N., and Leto, T.L. (1997). Specificity of p47phox SH3 domain interactions in NADPH oxidase assembly and activation. Mol. Cell. Biol. 17, 2177–2185.

    PubMed  Google Scholar 

  • De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D.U., Jin, R., Jones, J., Cong, R., and Franzoso, G. (2001). Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. Nature 414, 308–313.

    Article  PubMed  Google Scholar 

  • Degtyarenko, K.N., and Kulikova, T.A. (2001). Evolution of bioinorganic motifs in P450-containing systems. Biochem. Soc. Trans. 29, 139–147.

    Article  PubMed  CAS  Google Scholar 

  • DeLeo, F.R., Yu, L., Burritt, J.B., Loetterle, L.R., Bond, C.W., Jesaitis, A.J., and Quinn, M.T. (1995). Mapping sites of interaction of p47-phox and flavocytochrome b with random-sequence peptide phage display libraries. Proc. Natl. Acad. Sci. USA 92, 7110–7114.

    Article  PubMed  CAS  Google Scholar 

  • Deng, X., Gao, F., and May, W.S., Jr. (2003). Bcl2 retards G1/S cell cycle transition by regulating intracellular ROS. Blood 102, 3179–3185.

    Article  PubMed  CAS  Google Scholar 

  • Desaint, S., Luriau, S., Aude, J.C., Rousselet, G., and Toledano, M.B. (2004). Mammalian antioxidant defenses are not inducible by H2O2. J. Biol. Chem. 279, 31157–31163.

    Article  PubMed  CAS  Google Scholar 

  • Devin, A., Cook, A., Lin, Y., Rodriguez, Y., Kelliher, M., and Liu, Z. (2000). The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity 12, 419–429.

    Article  PubMed  CAS  Google Scholar 

  • Dinauer, M.C., Pierce, E.A., Bruns, G.A., Curnutte, J.T., and Orkin, S.H. (1990). Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease. J. Clin. Invest. 86, 1729–1737.

    CAS  Google Scholar 

  • Droge, W. (2002). Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47–95.

    PubMed  CAS  Google Scholar 

  • Dumont, P., Leu, J.I., Della Pietra, A.C., 3rd, George, D.L., and Murphy, M. (2003). The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 33, 357–365.

    Article  PubMed  CAS  Google Scholar 

  • Dupuy, C., Virion, A., Ohayon, R., Kaniewski, J., Deme, D., and Pommier, J. (1991). Mechanism of hydrogen peroxide formation catalyzed by NADPH oxidase in thyroid plasma membrane. J. Biol. Chem. 266, 3739–3743.

    PubMed  CAS  Google Scholar 

  • Dupuy, C., Virion, A., De Sandro, V., Ohayon, R., Kaniewski, J., Pommier, J., and Deme, D. (1992). Activation of the NADPHdependent H2O2-generating system in pig thyroid particulate fraction by limited proteolysis and Zn2+ treatment. Biochem. J. 283, 591–595.

    PubMed  CAS  Google Scholar 

  • Dupuy, C., Ohayon, R., Valent, A., Noel-Hudson, M.S., Deme, D., and Virion, A. (1999). Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas. J. Biol. Chem. 274, 37265–37269.

    Article  PubMed  CAS  Google Scholar 

  • Dupuy, C., Pomerance, M., Ohayon, R., Noel-Hudson, M.S., Deme, D., Chaaraoui, M., Francon, J., and Virion, A. (2000). Thyroid oxidase (THOX2) gene expression in the rat thyroid cell line FRTL-5. Biochem. Biophys. Res. Commun. 277, 287–292.

    Article  PubMed  CAS  Google Scholar 

  • El Benna, J., Faust, L.P., and Babior, B.M. (1994). The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases. J. Biol. Chem. 269, 23431–23436.

    PubMed  Google Scholar 

  • El Benna, J., Faust, R.P., Johnson, J.L., and Babior, B.M. (1996). Phosphorylation of the respiratory burst oxidase subunit p47- phox as determined by two-dimensional phosphopeptide mapping. Phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. J. Biol. Chem. 271, 6374–6378.

    Article  PubMed  Google Scholar 

  • El Hassani, R.A., Benfares, N., Caillou, B., Talbot, M., Sabourin, J.C., Belotte, V., Morand, S., Gnidehou, S., Agnandji, D., Ohayon, R., et al. (2005). Dual oxidase2 is expressed all along the digestive tract. Am. J. Physiol. Gastrointest Liver Physiol. 288, G933–942.

    Article  PubMed  CAS  Google Scholar 

  • Ellerby, L.M., Ellerby, H.M., Park, S.M., Holleran, A.L., Murphy, A.N., Fiskum, G., Kane, D.J., Testa, M.P., Kayalar, C., and Bredesen, D.E. (1996). Shift of the cellular oxidation-reduction potential in neural cells expressing Bcl-2. J. Neurochem. 67, 1259–1267.

    Google Scholar 

  • Ferrari, G., Yan, C.Y., and Greene, L.A. (1995). N-acetylcysteine (D- and L-stereoisomers) prevents apoptotic death of neuronal cells. J. Neurosci. 15, 2857–2866.

    PubMed  CAS  Google Scholar 

  • Finegold, A.A., Shatwell, K.P., Segal, A.W., Klausner, R.D., and Dancis, A. (1996). Intramembrane bis-heme motif for transmembrane electron transport conserved in a yeast iron reductase and the human NADPH oxidase. J. Biol. Chem. 271, 31021–31024.

    Article  PubMed  CAS  Google Scholar 

  • Finkel, T. (1998). Oxygen radicals and signaling. Curr. Opin. Cell Biol. 10, 248–253.

    Article  PubMed  CAS  Google Scholar 

  • Fontayne, A., Dang, P.M., Gougerot-Pocidalo, M.A., and El-Benna, J. (2002). Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry 41, 7743–7750.

    Article  PubMed  CAS  Google Scholar 

  • Forteza, R., Salathe, M., Miot, F., and Conner, G.E. (2005). Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 32, 462–469.

    Article  PubMed  CAS  Google Scholar 

  • Frost, J.A., Geppert, T.D., Cobb, M.H., and Feramisco, J.R. (1994). A requirement for extracellular signal-regulated kinase (ERK) function in the activation of AP-1 by Ha-Ras, phorbol 12-myristate 13-acetate, and serum. Proc. Natl. Acad. Sci. USA 91, 3844–3848.

    Article  PubMed  CAS  Google Scholar 

  • Galluzzi, L., Morselli, E., Kepp, O., Vitale, I., Rigoni, A., Vacchelli, E., Michaud, M., Zischka, H., Castedo, M., and Kroemer, G. (2010). Mitochondrial gateways to cancer. Mol. Aspects Med. 31, 1–20.

    Article  PubMed  CAS  Google Scholar 

  • Geiszt, M., Lekstrom, K., Witta, J., and Leto, T.L. (2003a). Proteins homologous to p47phox and p67phox support superoxide production by NAD(P)H oxidase 1 in colon epithelial cells. J. Biol. Chem. 278, 20006–20012.

    Article  PubMed  CAS  Google Scholar 

  • Geiszt, M., Witta, J., Baffi, J., Lekstrom, K., and Leto, T.L. (2003b). Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J. 17, 1502–1504.

    PubMed  CAS  Google Scholar 

  • Gertz, M., Fischer, F., Wolters, D., and Steegborn, C. (2008). Activation of the lifespan regulator p66Shc through reversible disulfide bond formation. Proc. Natl. Acad. Sci. USA 105, 5705–5709.

    Article  PubMed  CAS  Google Scholar 

  • Giaccia, A.J., and Kastan, M.B. (1998). The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev. 12, 2973–2983.

    Article  PubMed  CAS  Google Scholar 

  • Gianni, D., Taulet, N., DerMardirossian, C., and Bokoch, G.M. (2010). c-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells. Mol. Biol. Cell 21, 4287–4298.

    Article  PubMed  CAS  Google Scholar 

  • Gianni, D., DerMardirossian, C., and Bokoch, G.M. (2011). Direct interaction between Tks proteins and the N-terminal proline-rich region (PRR) of NoxA1 mediates Nox1-dependent ROS generation. Eur. J. Cell Biol. 90, 164–171.

    Article  PubMed  CAS  Google Scholar 

  • Giorgio, M., Migliaccio, E., Orsini, F., Paolucci, D., Moroni, M., Contursi, C., Pelliccia, G., Luzi, L., Minucci, S., Marcaccio, M., et al. (2005). Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122, 221–233.

    Article  PubMed  CAS  Google Scholar 

  • Gong, P., and Cederbaum, A.I. (2006). Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1. Hepatology 43, 144–153.

    Article  PubMed  CAS  Google Scholar 

  • Gorsky, L.D., Koop, D.R., and Coon, M.J. (1984). On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J. Biol. Chem. 259, 6812–6817.

    PubMed  CAS  Google Scholar 

  • Gottlieb, E., Vander Heiden, M.G., and Thompson, C.B. (2000). Bclx( L) prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis. Mol. Cell. Biol. 20, 5680–5689.

    Article  PubMed  CAS  Google Scholar 

  • Grasberger, H., and Refetoff, S. (2006). Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. J. Biol. Chem. 281, 18269–18272.

    Article  PubMed  CAS  Google Scholar 

  • Green, D.R., and Kroemer, G. (2004). The pathophysiology of mitochondrial cell death. Science 305, 626–629.

    Article  PubMed  CAS  Google Scholar 

  • Greene, L.A. (1978). Nerve growth factor prevents the death and stimulates the neuronal differentiation of clonal PC12 pheochromocytoma cells in serum-free medium. J. Cell Biol. 78, 747–755.

    Article  PubMed  CAS  Google Scholar 

  • Groemping, Y., Lapouge, K., Smerdon, S.J., and Rittinger, K. (2003). Molecular basis of phosphorylation-induced activation of the NADPH oxidase. Cell 113, 343–355.

    Article  PubMed  CAS  Google Scholar 

  • Guzy, R.D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K.D., Simon, M.C., Hammerling, U., and Schumacker, P.T. (2005). Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 1, 401–408.

    Article  PubMed  CAS  Google Scholar 

  • Hamanaka, R.B., and Chandel, N.S. (2010). Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem. Sci. 35, 505–513.

    Article  PubMed  CAS  Google Scholar 

  • Han, C.H., Freeman, J.L., Lee, T., Motalebi, S.A., and Lambeth, J.D. (1998). Regulation of the neutrophil respiratory burst oxidase. Identification of an activation domain in p67 (phox). J. Biol. Chem. 273, 16663–16668.

    Article  PubMed  CAS  Google Scholar 

  • Han, D., Ybanez, M.D., Ahmadi, S., Yeh, K., and Kaplowitz, N. (2009). Redox regulation of tumor necrosis factor signaling. Antioxid Redox Signal. 11, 2245–2263.

    Article  PubMed  CAS  Google Scholar 

  • Hansford, R.G., Hogue, B.A., and Mildaziene, V. (1997). Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J. Bioenerg. Biomembr. 29, 89–95.

    Article  PubMed  CAS  Google Scholar 

  • Hanukoglu, I. (2006). Antioxidant protective mechanisms against reactive oxygen species (ROS) generated by mitochondrial P450 systems in steroidogenic cells. Drug Metab. Rev. 38, 171–196.

    Article  PubMed  CAS  Google Scholar 

  • Hanukoglu, I., Suh, B.S., Himmelhoch, S., and Amsterdam, A. (1990). Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells. J. Cell Biol. 111, 1373–1381.

    Article  PubMed  CAS  Google Scholar 

  • Hata, K., Takeshige, K., and Sumimoto, H. (1997). Roles for proline-rich regions of p47phox and p67phox in the phagocyte NADPH oxidase activation in vitro. Biochem. Biophys. Res. Commun. 241, 226–231.

    Article  PubMed  CAS  Google Scholar 

  • Henderson, L.M., Chappell, J.B., and Jones, O.T. (1987). The super-oxide-generating NADPH oxidase of human neutrophils is electrogenic and associated with an H+ channel. Biochem. J. 246, 325–329.

    PubMed  CAS  Google Scholar 

  • Hockenbery, D.M., Oltvai, Z.N., Yin, X.M., Milliman, C.L., and Korsmeyer, S.J. (1993). Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75, 241–251.

    Article  PubMed  CAS  Google Scholar 

  • Hsu, H., Xiong, J., and Goeddel, D.V. (1995). The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81, 495–504.

    Article  PubMed  CAS  Google Scholar 

  • Hsu, H., Shu, H.B., Pan, M.G., and Goeddel, D.V. (1996). TRADDTRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299–308.

    Article  PubMed  CAS  Google Scholar 

  • Huang, J., Hitt, N.D., and Kleinberg, M.E. (1995). Stoichiometry of p22-phox and gp91-phox in phagocyte cytochrome b558. Biochemistry 34, 16753–16757.

    Article  PubMed  CAS  Google Scholar 

  • Huang, P., Feng, L., Oldham, E.A., Keating, M.J., and Plunkett, W. (2000). Superoxide dismutase as a target for the selective killing of cancer cells. Nature 407, 390–395.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, P.M., Bunz, F., Yu, J., Rago, C., Chan, T.A., Murphy, M.P., Kelso, G.F., Smith, R.A., Kinzler, K.W., and Vogelstein, B. (2001). Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells. Nat. Med. 7, 1111–1117.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, I.T., Chung, Y.M., Kim, J.J., Chung, J.S., Kim, B.S., Kim, H.J., Kim, J.S., and Yoo, Y.D. (2007). Drug resistance to 5-FU linked to reactive oxygen species modulator 1. Biochem. Biophys. Res. Commun. 359, 304–310.

    Article  PubMed  CAS  Google Scholar 

  • Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K., and Gotoh, Y. (1997). Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275, 90–94.

    Article  PubMed  CAS  Google Scholar 

  • Iwata, S., Lee, J.W., Okada, K., Lee, J.K., Iwata, M., Rasmussen, B., Link, T.A., Ramaswamy, S., and Jap, B.K. (1998). Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science 281, 64–71.

    Article  PubMed  CAS  Google Scholar 

  • Jagnandan, D., Church, J.E., Banfi, B., Stuehr, D.J., Marrero, M.B., and Fulton, D.J. (2007). Novel mechanism of activation of NADPH oxidase 5. calcium sensitization via phosphorylation. J. Biol. Chem. 282, 6494–6507.

    Article  PubMed  CAS  Google Scholar 

  • Jiang, Q., Griffin, D.A., Barofsky, D.F., and Hurst, J.K. (1997). Intraphagosomal chlorination dynamics and yields determined using unique fluorescent bacterial mimics. Chem. Res. Toxicol. 10, 1080–1089.

    Article  PubMed  CAS  Google Scholar 

  • Kanai, F., Liu, H., Field, S.J., Akbary, H., Matsuo, T., Brown, G.E., Cantley, L.C., and Yaffe, M.B. (2001). The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Nat. Cell Biol. 3, 675–678.

    Article  PubMed  CAS  Google Scholar 

  • Kane, D.J., Sarafian, T.A., Anton, R., Hahn, H., Gralla, E.B., Valentine, J.S., Ord, T., and Bredesen, D.E. (1993). Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274–1277.

    Article  PubMed  CAS  Google Scholar 

  • Karathanassis, D., Stahelin, R.V., Bravo, J., Perisic, O., Pacold, C.M., Cho, W., and Williams, R.L. (2002). Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction. EMBO J. 21, 5057–5068.

    Article  PubMed  CAS  Google Scholar 

  • Karin, M., and Lin, A. (2002). NF-kappaB at the crossroads of life and death. Nat. Immunol. 3, 221–227.

    Article  PubMed  CAS  Google Scholar 

  • Kawahara, T., Ritsick, D., Cheng, G., and Lambeth, J.D. (2005). Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation. J. Biol. Chem. 280, 31859–31869.

    Article  PubMed  CAS  Google Scholar 

  • Kawai, T., and Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384.

    Article  PubMed  CAS  Google Scholar 

  • Kim, R., Emi, M., Tanabe, K., Murakami, S., Uchida, Y., and Arihiro, K. (2006). Regulation and interplay of apoptotic and nonapoptotic cell death. J. Pathol. 208, 319–326.

    Article  PubMed  CAS  Google Scholar 

  • Kim, J.S., Diebold, B.A., Babior, B.M., Knaus, U.G., and Bokoch, G.M. (2007a). Regulation of Nox1 activity via protein kinase Amediated phosphorylation of NoxA1 and 14-3-3 binding. J. Biol. Chem. 282, 34787–34800.

    Article  PubMed  CAS  Google Scholar 

  • Kim, Y.S., Morgan, M.J., Choksi, S., and Liu, Z.G. (2007b). TNFinduced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol. Cell 26, 675–687.

    Article  PubMed  CAS  Google Scholar 

  • Kim, J.J., Lee, S.B., Park, J.K., and Yoo, Y.D. (2010). TNF-alpha induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L). Cell Death Differ. 17, 1420–1434.

    Article  PubMed  CAS  Google Scholar 

  • King, A.R., Francis, S.E., Bridgeman, C.J., Bird, H., Whyte, M.K., and Crossman, D.C. (2003). A role for caspase-1 in serum withdrawal-induced apoptosis of endothelial cells. Lab. Invest. 83, 1497–1508.

    Article  PubMed  CAS  Google Scholar 

  • Kirkland, R.A., and Franklin, J.L. (2001). Evidence for redox regulation of cytochrome C release during programmed neuronal death: antioxidant effects of protein synthesis and caspase inhibition. J. Neurosci. 21, 1949–1963.

    PubMed  CAS  Google Scholar 

  • Kirkland, R.A., Windelborn, J.A., Kasprzak, J.M., and Franklin, J.L. (2002). A Bax-induced pro-oxidant state is critical for cytochrome c release during programmed neuronal death. J. Neurosci. 22, 6480–6490.

    PubMed  CAS  Google Scholar 

  • Kiss, P.J., Knisz, J., Zhang, Y., Baltrusaitis, J., Sigmund, C.D., Thalmann, R., Smith, R.J., Verpy, E., and Banfi, B. (2006). Inactivation of NADPH oxidase organizer 1 results in severe imbalance. Curr. Biol. 16, 208–213.

    Article  PubMed  CAS  Google Scholar 

  • Knaus, U.G., Heyworth, P.G., Evans, T., Curnutte, J.T., and Bokoch, G.M. (1991). Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254, 1512–1515.

    Article  PubMed  CAS  Google Scholar 

  • Koga, H., Terasawa, H., Nunoi, H., Takeshige, K., Inagaki, F., and Sumimoto, H. (1999). Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J. Biol. Chem. 274, 25051–25060.

    Article  PubMed  CAS  Google Scholar 

  • Kong, Q., Beel, J.A., and Lillehei, K.O. (2000). A threshold concept for cancer therapy. Med. Hypotheses 55, 29–35.

    Article  PubMed  CAS  Google Scholar 

  • Kowaltowski, A.J., de Souza-Pinto, N.C., Castilho, R.F., and Vercesi, A.E. (2009). Mitochondria and reactive oxygen species. Free Radic. Biol. Med. 47, 333–343.

    Article  PubMed  CAS  Google Scholar 

  • Kroviarski, Y., Debbabi, M., Bachoual, R., Perianin, A., Gougerot-Pocidalo, M.A., El-Benna, J., and Dang, P.M. (2010). Phosphorylation of NADPH oxidase activator 1 (NOXA1) on serine 282 by MAP kinases and on serine 172 by protein kinase C and protein kinase A prevents NOX1 hyperactivation. FASEB J. 24, 2077–2092.

    Article  PubMed  CAS  Google Scholar 

  • Ksenzenko, M., Konstantinov, A.A., Khomutov, G.B., Tikhonov, A.N., and Ruuge, E.K. (1983). Effect of electron transfer inhibitors on superoxide generation in the cytochrome bc1 site of the mitochondrial respiratory chain. FEBS Lett. 155, 19–24.

    Article  PubMed  CAS  Google Scholar 

  • Kudin, A.P., Bimpong-Buta, N.Y., Vielhaber, S., Elger, C.E., and Kunz, W.S. (2004). Characterization of superoxide-producing sites in isolated brain mitochondria. J. Biol. Chem. 279, 4127–4135.

    Article  PubMed  CAS  Google Scholar 

  • Kuribayashi, F., Nunoi, H., Wakamatsu, K., Tsunawaki, S., Sato, K., Ito, T., and Sumimoto, H. (2002). The adaptor protein p40(phox) as a positive regulator of the superoxide-producing phagocyte oxidase. EMBO J. 21, 6312–6320.

    Article  PubMed  CAS  Google Scholar 

  • Kushnareva, Y., Murphy, A.N., and Andreyev, A. (2002). Complex Imediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation-reduction state. Biochem. J. 368, 545–553.

    Article  PubMed  CAS  Google Scholar 

  • Kutter, D., Devaquet, P., Vanderstocken, G., Paulus, J.M., Marchal, V., and Gothot, A. (2000). Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit? Acta Haematol. 104, 10–15.

    Article  PubMed  CAS  Google Scholar 

  • Kwong, L.K., and Sohal, R.S. (1998). Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria. Arch. Biochem. Biophys. 350, 118–126.

    Article  PubMed  CAS  Google Scholar 

  • Lamb, J.R., Tugendreich, S., and Hieter, P. (1995). Tetratrico peptide repeat interactions: to TPR or not to TPR? Trends Biochem. Sci. 20, 257–259.

    Article  PubMed  CAS  Google Scholar 

  • Lambert, A.J., and Brand, M.D. (2004). Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Biochem. J. 382, 511–517.

    Article  PubMed  CAS  Google Scholar 

  • Lapouge, K., Smith, S.J., Walker, P.A., Gamblin, S.J., Smerdon, S.J., and Rittinger, K. (2000). Structure of the TPR domain of p67phox in complex with Rac. GTP. Mol. Cell 6, 899–907.

    PubMed  CAS  Google Scholar 

  • Laurent, A., Nicco, C., Chereau, C., Goulvestre, C., Alexandre, J., Alves, A., Levy, E., Goldwasser, F., Panis, Y., Soubrane, O., et al. (2005). Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 65, 948–956.

    PubMed  CAS  Google Scholar 

  • Lee, S.B., Kim, J.J., Kim, T.W., Kim, B.S., Lee, M.S., and Yoo, Y.D. (2010). Serum deprivation-induced reactive oxygen species production is mediated by Romo1. Apoptosis 15, 204–218.

    Article  PubMed  CAS  Google Scholar 

  • Lee, S.B., Kim, J.J., Chung, J.S., Lee, M.S., Lee, K.H., Kim, B.S., and Yoo, Y.D. (2011). Romo1 is a negative-feedback regulator of Myc. J. Cell Sci. 124, 1911–1924.

    Article  PubMed  CAS  Google Scholar 

  • Leseney, A.M., Deme, D., Legue, O., Ohayon, R., Chanson, P., Sales, J.P., Carvalho, D.P., Dupuy, C., and Virion, A. (1999). Biochemical characterization of a Ca2+/NAD(P)H-dependent H2O2 generator in human thyroid tissue. Biochimie 81, 373–380.

    Article  PubMed  CAS  Google Scholar 

  • Leto, T.L., Adams, A.G., and de Mendez, I. (1994). Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline-rich targets. Proc. Natl. Acad. Sci. USA 91, 10650–10654.

    Article  PubMed  CAS  Google Scholar 

  • Leu, J.I., Dumont, P., Hafey, M., Murphy, M.E., and George, D.L. (2004). Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat. Cell Biol. 6, 443–450.

    Article  PubMed  CAS  Google Scholar 

  • Levine, A.J. (1997). p53, the cellular gatekeeper for growth and division. Cell 88, 323–331.

    Article  PubMed  CAS  Google Scholar 

  • Liu, S.L., Lin, X., Shi, D.Y., Cheng, J., Wu, C.Q., and Zhang, Y.D. (2002a). Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways. Arch. Biochem. Biophys. 406, 173–182.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y., Fiskum, G., and Schubert, D. (2002b). Generation of reactive oxygen species by the mitochondrial electron transport chain. J. Neurochem. 80, 780–787.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Z., Lu, H., Shi, H., Du, Y., Yu, J., Gu, S., Chen, X., Liu, K.J., and Hu, C.A. (2005). PUMA overexpression induces reactive oxygen species generation and proteasome-mediated stathmin degradation in colorectal cancer cells. Cancer Res. 65, 1647–1654.

    Article  PubMed  CAS  Google Scholar 

  • Lo, Y.Y., and Cruz, T.F. (1995). Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. J. Biol. Chem. 270, 11727–11730.

    Article  PubMed  CAS  Google Scholar 

  • Locksley, R.M., Killeen, N., and Lenardo, M.J. (2001). The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487–501.

    Article  PubMed  CAS  Google Scholar 

  • Loschen, G., Azzi, A., and Flohe, L. (1973). Mitochondrial H2O2 formation: relationship with energy conservation. FEBS Lett. 33, 84–87.

    Article  PubMed  CAS  Google Scholar 

  • Luxen, S., Belinsky, S.A., and Knaus, U.G. (2008). Silencing of DUOX NADPH oxidases by promoter hypermethylation in lung cancer. Cancer Res. 68, 1037–1045.

    Article  PubMed  CAS  Google Scholar 

  • Lyle, A.N., Deshpande, N.N., Taniyama, Y., Seidel-Rogol, B., Pounkova, L., Du, P., Papaharalambus, C., Lassegue, B., and Griendling, K.K. (2009). Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ. Res. 105, 249–259.

    Article  PubMed  CAS  Google Scholar 

  • Mansfield, K.D., Guzy, R.D., Pan, Y., Young, R.M., Cash, T.P., Schumacker, P.T., and Simon, M.C. (2005). Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab. 1, 393–399.

    Article  PubMed  CAS  Google Scholar 

  • Marchenko, N.D., Wolff, S., Erster, S., Becker, K., and Moll, U.M. (2007). Monoubiquitylation promotes mitochondrial p53 translocation. EMBO J. 26, 923–934.

    Article  PubMed  CAS  Google Scholar 

  • Marcillat, O., Zhang, Y., and Davies, K.J. (1989). Oxidative and non-oxidative mechanisms in the inactivation of cardiac mitochondrial electron transport chain components by doxorubicin. Biochem. J. 259, 181–189.

    PubMed  CAS  Google Scholar 

  • Martindale, J.L., and Holbrook, N.J. (2002). Cellular response to oxidative stress: signaling for suicide and survival. J. Cell Physiol. 192, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Martyn, K.D., Kim, M.J., Quinn, M.T., Dinauer, M.C., and Knaus, U.G. (2005). p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils. Blood 106, 3962–3969.

    Article  PubMed  CAS  Google Scholar 

  • Martyn, K.D., Frederick, L.M., von Loehneysen, K., Dinauer, M.C., and Knaus, U.G. (2006). Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell. Signal. 18, 69–82.

    Article  PubMed  CAS  Google Scholar 

  • Matsuzawa, A., and Ichijo, H. (2005). Stress-responsive protein kinases in redox-regulated apoptosis signaling. Antioxid Redox Signal. 7, 472–481.

    Article  PubMed  CAS  Google Scholar 

  • McKinnon, R.A., and McManus, M.E. (1996). Localization of cytochromes P450 in human tissues: implications for chemical toxicity. Pathology 28, 148–155.

    Article  PubMed  CAS  Google Scholar 

  • Meier, B., Radeke, H.H., Selle, S., Younes, M., Sies, H., Resch, K., and Habermehl, G.G. (1989). Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem. J. 263, 539–545.

    PubMed  CAS  Google Scholar 

  • Meitzler, J.L., and Ortiz de Montellano, P.R. (2009). Caenorhabditis elegans and human dual oxidase 1 (DUOX1) “peroxidase” domains: insights into heme binding and catalytic activity. J. Biol. Chem. 284, 18634–18643.

    Article  PubMed  CAS  Google Scholar 

  • Micheau, O., and Tschopp, J. (2003). Induction of TNF receptor Imediated apoptosis via two sequential signaling complexes. Cell 114, 181–190.

    Article  PubMed  CAS  Google Scholar 

  • Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P.P., Lanfrancone, L., and Pelicci, P.G. (1999). The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309–313.

    Article  PubMed  CAS  Google Scholar 

  • Mihara, M., Erster, S., Zaika, A., Petrenko, O., Chittenden, T., Pancoska, P., and Moll, U.M. (2003). p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11, 577–590.

    Article  PubMed  CAS  Google Scholar 

  • Miller, Y.I., Viriyakosol, S., Binder, C.J., Feramisco, J.R., Kirkland, T.N., and Witztum, J.L. (2003). Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J. Biol. Chem. 278, 1561–1568.

    Article  PubMed  CAS  Google Scholar 

  • Miller, Y.I., Viriyakosol, S., Worrall, D.S., Boullier, A., Butler, S., and Witztum, J.L. (2005). Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized lowdensity lipoprotein in macrophages. Arterioscler Thromb. Vasc. Biol. 25, 1213–1219.

    Article  PubMed  CAS  Google Scholar 

  • Miwa, S., and Brand, M.D. (2005). The topology of superoxide production by complex III and glycerol 3-phosphate dehydrogenase in Drosophila mitochondria. Biochim. Biophys. Acta 1709, 214–219.

    Article  PubMed  CAS  Google Scholar 

  • Miyajima, A., Nakashima, J., Yoshioka, K., Tachibana, M., Tazaki, H., and Murai, M. (1997). Role of reactive oxygen species in cisdichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells. Br. J. Cancer 76, 206–210.

    Article  PubMed  CAS  Google Scholar 

  • Miyano, K., Koga, H., Minakami, R., and Sumimoto, H. (2009). The insert region of the Rac GTPases is dispensable for activation of superoxide-producing NADPH oxidases. Biochem. J. 422, 373–382.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno, T., Kaibuchi, K., Ando, S., Musha, T., Hiraoka, K., Takaishi, K., Asada, M., Nunoi, H., Matsuda, I., and Takai, Y. (1992). Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. J. Biol. Chem. 267, 10215–10218.

    PubMed  CAS  Google Scholar 

  • Morand, S., Ueyama, T., Tsujibe, S., Saito, N., Korzeniowska, A., and Leto, T.L. (2009). Duox maturation factors form cell surface complexes with Duox affecting the specificity of reactive oxygen species generation. FASEB J. 23, 1205–1218.

    Article  PubMed  CAS  Google Scholar 

  • Moreno, J.C., Bikker, H., Kempers, M.J., van Trotsenburg, A.S., Baas, F., de Vijlder, J.J., Vulsma, T., and Ris-Stalpers, C. (2002). Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N. Engl. J. Med. 347, 95–102.

    Article  PubMed  CAS  Google Scholar 

  • Moskwa, P., Lorentzen, D., Excoffon, K.J., Zabner, J., McCray, P.B., Jr., Nauseef, W.M., Dupuy, C., and Banfi, B. (2007). A novel host defense system of airways is defective in cystic fibrosis. Am. J. Respir. Crit. Care Med. 175, 174–183.

    Article  PubMed  CAS  Google Scholar 

  • Mouche, S., Mkaddem, S.B., Wang, W., Katic, M., Tseng, Y.H., Carnesecchi, S., Steger, K., Foti, M., Meier, C.A., Muzzin, P., et al. (2007). Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation. Biochim. Biophys. Acta 1773, 1015–1027.

    Article  PubMed  CAS  Google Scholar 

  • Muller, F.L., Liu, Y., and Van Remmen, H. (2004). Complex III releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem. 279, 49064–49073.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, M.P. (2009). How mitochondria produce reactive oxygen species. Biochem. J. 417, 1–13.

    Article  PubMed  CAS  Google Scholar 

  • Na, A.R., Chung, Y.M., Lee, S.B., Park, S.H., Lee, M.S., and Yoo, Y.D. (2008). A critical role for Romo1-derived ROS in cell proliferation. Biochem. Biophys. Res. Commun. 369, 672–678.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, Y., Ohtaki, S., Makino, R., Tanaka, T., and Ishimura, Y. (1989). Superoxide anion is the initial product in the hydrogen peroxide formation catalyzed by NADPH oxidase in porcine thyroid plasma membrane. J. Biol. Chem. 264, 4759–4761.

    PubMed  CAS  Google Scholar 

  • Nakamura, Y., Makino, R., Tanaka, T., Ishimura, Y., and Ohtaki, S. (1991). Mechanism of H2O2 production in porcine thyroid cells: evidence for intermediary formation of superoxide anion by NADPH-dependent H2O2-generating machinery. Biochemistry 30, 4880–4886.

    Article  PubMed  CAS  Google Scholar 

  • Nakano, Y., Longo-Guess, C.M., Bergstrom, D.E., Nauseef, W.M., Jones, S.M., and Banfi, B. (2008). Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice. J. Clin. Invest. 118, 1176–1185.

    PubMed  CAS  Google Scholar 

  • Nemoto, S., Combs, C.A., French, S., Ahn, B.H., Fergusson, M.M., Balaban, R.S., and Finkel, T. (2006). The mammalian longevityassociated gene product p66shc regulates mitochondrial metabolism. J. Biol. Chem. 281, 10555–10560.

    Article  PubMed  CAS  Google Scholar 

  • Ni, W., Zhan, Y., He, H., Maynard, E., Balschi, J.A., and Oettgen, P. (2007). Ets-1 is a critical transcriptional regulator of reactive oxygen species and p47(phox) gene expression in response to angiotensin II. Circ. Res. 101, 985–994.

    Article  PubMed  CAS  Google Scholar 

  • Oh, H., Jung, H.Y., Kim, J., and Bae, Y.S. (2010). Phosphorylation of serine282 in NADPH oxidase activator 1 by Erk desensitizes EGF-induced ROS generation. Biochem. Biophys. Res. Commun. 394, 691–696.

    Article  PubMed  CAS  Google Scholar 

  • Okado-Matsumoto, A., and Fridovich, I. (2001). Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD in mitochondria. J. Biol. Chem. 276, 38388–38393.

    Article  PubMed  CAS  Google Scholar 

  • Pachucki, J., Wang, D., Christophe, D., and Miot, F. (2004). Structural and functional characterization of the two human ThOX/Duox genes and their 5′-flanking regions. Mol. Cell. Endocrinol. 214, 53–62.

    Article  PubMed  CAS  Google Scholar 

  • Pacquelet, S., Lehmann, M., Luxen, S., Regazzoni, K., Frausto, M., Noack, D., and Knaus, U.G. (2008). Inhibitory action of NoxA1 on dual oxidase activity in airway cells. J. Biol. Chem. 283, 24649–24658.

    Article  PubMed  CAS  Google Scholar 

  • Paffenholz, R., Bergstrom, R.A., Pasutto, F., Wabnitz, P., Munroe, R.J., Jagla, W., Heinzmann, U., Marquardt, A., Bareiss, A., Laufs, J., et al. (2004). Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev. 18, 486–491.

    Article  PubMed  CAS  Google Scholar 

  • Pandey, S., Lopez, C., and Jammu, A. (2003). Oxidative stress and activation of proteasome protease during serum deprivationinduced apoptosis in rat hepatoma cells; inhibition of cell death by melatonin. Apoptosis 8, 497–508.

    Article  PubMed  CAS  Google Scholar 

  • Pandey, D., Gratton, J.P., Rafikov, R., Black, S.M., and Fulton, D.J. (2011). Calcium/calmodulin-dependent kinase II mediates the phosphorylation and activation of NADPH oxidase 5. Mol. Pharmacol. 80, 407–415.

    Article  PubMed  CAS  Google Scholar 

  • Papa, S., Zazzeroni, F., Bubici, C., Jayawardena, S., Alvarez, K., Matsuda, S., Nguyen, D.U., Pham, C.G., Nelsbach, A.H., Melis, T., et al. (2004). Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2. Nat. Cell Biol. 6, 146–153.

    Article  PubMed  CAS  Google Scholar 

  • Park, H.S., Lee, S.H., Park, D., Lee, J.S., Ryu, S.H., Lee, W.J., Rhee, S.G., and Bae, Y.S. (2004). Sequential activation of phosphatidylinositol 3-kinase, beta Pix, Rac1, and Nox1 in growth factor-induced production of H2O2. Mol. Cell. Biol. 24, 4384–4394.

    Article  PubMed  CAS  Google Scholar 

  • Park, H.S., Chun, J.N., Jung, H.Y., Choi, C., and Bae, Y.S. (2006a). Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells. Cardiovasc. Res. 72, 447–455.

    Article  PubMed  CAS  Google Scholar 

  • Park, H.S., Park, D., and Bae, Y.S. (2006b). Molecular interaction of NADPH oxidase 1 with betaPix and Nox organizer 1. Biochem. Biophys. Res. Commun. 339, 985–990.

    Article  PubMed  CAS  Google Scholar 

  • Parkos, C.A., Dinauer, M.C., Jesaitis, A.J., Orkin, S.H., and Curnutte, J.T. (1989). Absence of both the 91kD and 22kD subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease. Blood 73, 1416–1420.

    PubMed  CAS  Google Scholar 

  • Patel, D.N., Bailey, S.R., Gresham, J.K., Schuchman, D.B., Shelhamer, J.H., Goldstein, B.J., Foxwell, B.M., Stemerman, M.B., Maranchie, J.K., Valente, A.J., et al. (2006). TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells. Biochem. Biophys. Res. Commun. 347, 1113–1120.

    Article  PubMed  CAS  Google Scholar 

  • Pelicano, H., Feng, L., Zhou, Y., Carew, J.S., Hileman, E.O., Plunkett, W., Keating, M.J., and Huang, P. (2003). Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. J. Biol. Chem. 278, 37832–37839.

    Article  PubMed  CAS  Google Scholar 

  • Pelicano, H., Carney, D., and Huang, P. (2004). ROS stress in cancer cells and therapeutic implications. Drug Resist. Updat. 7, 97–110.

    Article  PubMed  CAS  Google Scholar 

  • Pelicci, G., Lanfrancone, L., Grignani, F., McGlade, J., Cavallo, F., Forni, G., Nicoletti, I., Pawson, T., and Pelicci, P.G. (1992). A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell 70, 93–104.

    Article  PubMed  CAS  Google Scholar 

  • Pham, C.G., Bubici, C., Zazzeroni, F., Papa, S., Jones, J., Alvarez, K., Jayawardena, S., De Smaele, E., Cong, R., Beaumont, C., et al. (2004). Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119, 529–542.

    Article  PubMed  CAS  Google Scholar 

  • Pim, D., and Banks, L. (2004). p53 polymorphic variants at codon 72 exert different effects on cell cycle progression. Int. J. Cancer 108, 196–199.

    Article  PubMed  CAS  Google Scholar 

  • Pinton, P., Rimessi, A., Marchi, S., Orsini, F., Migliaccio, E., Giorgio, M., Contursi, C., Minucci, S., Mantovani, F., Wieckowski, M.R., et al. (2007). Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315, 659–663.

    Article  PubMed  CAS  Google Scholar 

  • Polyak, K., Xia, Y., Zweier, J.L., Kinzler, K.W., and Vogelstein, B. (1997). A model for p53-induced apoptosis. Nature 389, 300–305.

    Article  PubMed  CAS  Google Scholar 

  • Ponting, C.P. (1996). Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains? Protein Sci. 5, 2353–2357.

    Article  PubMed  CAS  Google Scholar 

  • Poyton, R.O., Ball, K.A., and Castello, P.R. (2009). Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol. Metab. 20, 332–340.

    Article  PubMed  CAS  Google Scholar 

  • Price, M.O., McPhail, L.C., Lambeth, J.D., Han, C.H., Knaus, U.G., and Dinauer, M.C. (2002). Creation of a genetic system for analysis of the phagocyte respiratory burst: high-level reconstitution of the NADPH oxidase in a nonhematopoietic system. Blood 99, 2653–2661.

    Article  PubMed  CAS  Google Scholar 

  • Reed, J.C. (2006). Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ. 13, 1378–1386.

    Article  PubMed  CAS  Google Scholar 

  • Reeves, E.P., Lu, H., Jacobs, H.L., Messina, C.G., Bolsover, S., Gabella, G., Potma, E.O., Warley, A., Roes, J., and Segal, A.W. (2002). Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291–297.

    Article  PubMed  CAS  Google Scholar 

  • Rhee, S.G., and Woo, H.A. (2011). Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger HO, and protein chaperones. Antioxid Redox Signal. 15, 781–794.

    Article  PubMed  CAS  Google Scholar 

  • Rigutto, S., Hoste, C., Grasberger, H., Milenkovic, M., Communi, D., Dumont, J.E., Corvilain, B., Miot, F., and De Deken, X. (2009). Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation. J. Biol. Chem. 284, 6725–6734.

    Article  PubMed  CAS  Google Scholar 

  • Rittle, J., and Green, M.T. (2010). Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330, 933–937.

    Article  PubMed  CAS  Google Scholar 

  • Rivera, A., and Maxwell, S.A. (2005). The p53-induced gene-6 (proline oxidase) mediates apoptosis through a calcineurin-dependent pathway. J. Biol. Chem. 280, 29346–29354.

    Article  PubMed  CAS  Google Scholar 

  • Rokutan, K., Kawahara, T., Kuwano, Y., Tominaga, K., Sekiyama, A., and Teshima-Kondo, S. (2006). NADPH oxidases in the gastrointestinal tract: a potential role of Nox1 in innate immune response and carcinogenesis. Antioxid Redox Signal. 8, 1573–1582.

    Article  PubMed  CAS  Google Scholar 

  • Rong, Y., and Distelhorst, C.W. (2008). Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Annu. Rev. Physiol. 70, 73–91.

    Article  PubMed  CAS  Google Scholar 

  • Rothe, M., Wong, S.C., Henzel, W.J., and Goeddel, D.V. (1994). A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78, 681–692.

    Article  PubMed  CAS  Google Scholar 

  • Rouhanizadeh, M., Hwang, J., Clempus, R.E., Marcu, L., Lassegue, B., Sevanian, A., and Hsiai, T.K. (2005). Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine induces vascular endothelial superoxide production: implication of NADPH oxidase. Free Radic. Biol. Med. 39, 1512–1522.

    Article  PubMed  CAS  Google Scholar 

  • Sablina, A.A., Budanov, A.V., Ilyinskaya, G.V., Agapova, L.S., Kravchenko, J.E., and Chumakov, P.M. (2005). The antioxidant function of the p53 tumor suppressor. Nat. Med. 11, 1306–1313.

    Article  PubMed  CAS  Google Scholar 

  • Sakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., Piao, J.H., Yagita, H., Okumura, K., Doi, T., et al. (2003). NFkappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J. 22, 3898–3909.

    Article  PubMed  CAS  Google Scholar 

  • Sansome, C., Zaika, A., Marchenko, N.D., and Moll, U.M. (2001). Hypoxia death stimulus induces translocation of p53 protein to mitochondria. Detection by immunofluorescence on whole cells. FEBS Lett. 488, 110–115.

    Article  PubMed  CAS  Google Scholar 

  • Satoh, T., Sakai, N., Enokido, Y., Uchiyama, Y., and Hatanaka, H. (1996). Survival factor-insensitive generation of reactive oxygen species induced by serum deprivation in neuronal cells. Brain Res. 733, 9–14.

    Article  PubMed  CAS  Google Scholar 

  • Schleiss, M.B., Holz, O., Behnke, M., Richter, K., Magnussen, H., and Jorres, R.A. (2000). The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate. Eur. Respir. J. 16, 1115–1118.

    Article  PubMed  CAS  Google Scholar 

  • Schrenzel, J., Serrander, L., Banfi, B., Nusse, O., Fouyouzi, R., Lew, D.P., Demaurex, N., and Krause, K.H. (1998). Electron currents generated by the human phagocyte NADPH oxidase. Nature 392, 734–737.

    Article  PubMed  CAS  Google Scholar 

  • Schroder, K., Helmcke, I., Palfi, K., Krause, K.H., Busse, R., and Brandes, R.P. (2007). Nox1 mediates basic fibroblast growth factor-induced migration of vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 27, 1736–1743.

    Article  PubMed  CAS  Google Scholar 

  • Segal, A.W. (2005). How neutrophils kill microbes. Annu. Rev. Immunol. 23, 197–223.

    Article  PubMed  CAS  Google Scholar 

  • Segal, A.W., West, I., Wientjes, F., Nugent, J.H., Chavan, A.J., Haley, B., Garcia, R.C., Rosen, H., and Scrace, G. (1992). Cytochrome b-245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes. Biochem. J. 284(Pt 3), 781–788.

    PubMed  CAS  Google Scholar 

  • Sekharam, M., Trotti, A., Cunnick, J.M., and Wu, J. (1998). Suppression of fibroblast cell cycle progression in G1 phase by Nacetylcysteine. Toxicol. Appl. Pharmacol. 149, 210–216.

    Article  PubMed  CAS  Google Scholar 

  • Shoji, Y., Uedono, Y., Ishikura, H., Takeyama, N., and Tanaka, T. (1995). DNA damage induced by tumour necrosis factor-alpha in L929 cells is mediated by mitochondrial oxygen radical formation. Immunology 84, 543–548.

    PubMed  CAS  Google Scholar 

  • Sigaud, S., Evelson, P., and Gonzalez-Flecha, B. (2005). H2O2-induced proliferation of primary alveolar epithelial cells is mediated by MAP kinases. Antioxid Redox Signal. 7, 6–13.

    Article  PubMed  CAS  Google Scholar 

  • Spat, A., and Hunyady, L. (2004). Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Physiol. Rev. 84, 489–539.

    Article  PubMed  CAS  Google Scholar 

  • St-Pierre, J., Buckingham, J.A., Roebuck, S.J., and Brand, M.D. (2002). Topology of superoxide production from different sites in the mitochondrial electron transport chain. J. Biol. Chem. 277, 44784–44790.

    Article  PubMed  CAS  Google Scholar 

  • Stahelin, R.V., Burian, A., Bruzik, K.S., Murray, D., and Cho, W. (2003). Membrane binding mechanisms of the PX domains of NADPH oxidase p40phox and p47phox. J. Biol. Chem. 278, 14469–14479.

    Article  PubMed  CAS  Google Scholar 

  • Stambolsky, P., Weisz, L., Shats, I., Klein, Y., Goldfinger, N., Oren, M., and Rotter, V. (2006). Regulation of AIF expression by p53. Cell Death Differ. 13, 2140–2149.

    Article  PubMed  CAS  Google Scholar 

  • Stasia, M.J., Bordigoni, P., Martel, C., and Morel, F. (2002). A novel and unusual case of chronic granulomatous disease in a child with a homozygous 36-bp deletion in the CYBA gene (A22 (0)) leading to the activation of a cryptic splice site in intron 4. Hum. Genet. 110, 444–450.

    Article  PubMed  Google Scholar 

  • Stone, J.R., and Collins, T. (2002). The role of hydrogen peroxide in endothelial proliferative responses. Endothelium 9, 231–238.

    Article  PubMed  CAS  Google Scholar 

  • Stone, J.R., and Yang, S. (2006). Hydrogen peroxide: a signaling messenger. Antioxid. Redox Signal. 8, 243–270.

    Article  PubMed  CAS  Google Scholar 

  • Sturtz, L.A., Diekert, K., Jensen, L.T., Lill, R., and Culotta, V.C. (2001). A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J. Biol. Chem. 276, 38084–38089.

    PubMed  CAS  Google Scholar 

  • Suh, Y.A., Arnold, R.S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A.B., Griendling, K.K., and Lambeth, J.D. (1999). Cell transformation by the superoxide-generating oxidase Mox1. Nature 401, 79–82.

    Article  PubMed  CAS  Google Scholar 

  • Sulciner, D.J., Irani, K., Yu, Z.X., Ferrans, V.J., Goldschmidt-Clermont, P., and Finkel, T. (1996). rac1 regulates a cytokinestimulated, redox-dependent pathway necessary for NF-kappaB activation. Mol. Cell. Biol. 16, 7115–7121.

    PubMed  CAS  Google Scholar 

  • Sumimoto, H., Sakamoto, N., Nozaki, M., Sakaki, Y., Takeshige, K., and Minakami, S. (1992). Cytochrome b558, a component of the phagocyte NADPH oxidase, is a flavoprotein. Biochem. Biophys. Res. Commun. 186, 1368–1375.

    Article  PubMed  CAS  Google Scholar 

  • Sundaresan, M., Yu, Z.X., Ferrans, V.J., Irani, K., and Finkel, T. (1995). Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270, 296–299.

    Article  PubMed  CAS  Google Scholar 

  • Szatrowski, T.P., and Nathan, C.F. (1991). Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51, 794–798.

    PubMed  CAS  Google Scholar 

  • Tabcharani, J.A., Rommens, J.M., Hou, Y.X., Chang, X.B., Tsui, L.C., Riordan, J.R., and Hanrahan, J.W. (1993). Multi-ion pore behaviour in the CFTR chloride channel. Nature 366, 79–82.

    Article  PubMed  CAS  Google Scholar 

  • Takeya, R., Ueno, N., Kami, K., Taura, M., Kohjima, M., Izaki, T., Nunoi, H., and Sumimoto, H. (2003). Novel human homologues of p47phox and p67phox participate in activation of superoxideproducing NADPH oxidases. J. Biol. Chem. 278, 25234–25246.

    Article  PubMed  CAS  Google Scholar 

  • Tan, S., Sagara, Y., Liu, Y., Maher, P., and Schubert, D. (1998). The regulation of reactive oxygen species production during programmed cell death. J. Cell Biol. 141, 1423–1432.

    Article  PubMed  CAS  Google Scholar 

  • Tang, G., Minemoto, Y., Dibling, B., Purcell, N.H., Li, Z., Karin, M., and Lin, A. (2001). Inhibition of JNK activation through NFkappaB target genes. Nature 414, 313–317.

    Article  PubMed  CAS  Google Scholar 

  • Tirone, F., and Cox, J.A. (2007). NADPH oxidase 5 (NOX5) interacts with and is regulated by calmodulin. FEBS Lett. 581, 1202–1208.

    Article  PubMed  CAS  Google Scholar 

  • Tomko, R.J., Jr., Bansal, P., and Lazo, J.S. (2006). Airing out an antioxidant role for the tumor suppressor p53. Mol. Interv. 6, 23–25, 22.

    Article  PubMed  CAS  Google Scholar 

  • Trinei, M., Giorgio, M., Cicalese, A., Barozzi, S., Ventura, A., Migliaccio, E., Milia, E., Padura, I.M., Raker, V.A., Maccarana, M., et al. (2002). A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21, 3872–3878.

    Article  PubMed  CAS  Google Scholar 

  • Turrens, J.F., Alexandre, A., and Lehninger, A.L. (1985). Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch. Biochem. Biophys. 237, 408–414.

    Article  PubMed  CAS  Google Scholar 

  • Ueno, N., Takeya, R., Miyano, K., Kikuchi, H., and Sumimoto, H. (2005). The NADPH oxidase Nox3 constitutively produces super-oxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J. Biol. Chem. 280, 23328–23339.

    Article  PubMed  CAS  Google Scholar 

  • Ueyama, T., Geiszt, M., and Leto, T.L. (2006). Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases. Mol. Cell. Biol. 26, 2160–2174.

    Article  PubMed  CAS  Google Scholar 

  • Ueyama, T., Tatsuno, T., Kawasaki, T., Tsujibe, S., Shirai, Y., Sumimoto, H., Leto, T.L., and Saito, N. (2007). A regulated adaptor function of p40phox: distinct p67phox membrane targeting by p40phox and by p47phox. Mol. Biol. Cell 18, 441–454.

    Article  PubMed  CAS  Google Scholar 

  • Valko, M., Rhodes, C.J., Moncol, J., Izakovic, M., and Mazur, M. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 160, 1–40.

    Article  PubMed  CAS  Google Scholar 

  • van der Valk, J., Mellor, D., Brands, R., Fischer, R., Gruber, F., Gstraunthaler, G., Hellebrekers, L., Hyllner, J., Jonker, F.H., Prieto, P., et al. (2004). The humane collection of fetal bovine serum and possibilities for serum-free cell and tissue culture. Toxicol. In Vitro 18, 1–12.

    Article  PubMed  CAS  Google Scholar 

  • Vander Heiden, M.G., Chandel, N.S., Williamson, E.K., Schumacker, P.T., and Thompson, C.B. (1997). Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 91, 627–637.

    Article  Google Scholar 

  • Venditti, P., Daniele, C.M., De Leo, T., and Di Meo, S. (1998). Effect of phenobarbital treatment on characteristics determining susceptibility to oxidants of homogenates, mitochondria and microsomes from rat liver. Cell Physiol. Biochem. 8, 328–338.

    Article  PubMed  CAS  Google Scholar 

  • Verkman, A.S., Song, Y., and Thiagarajah, J.R. (2003). Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Am. J. Physiol. Cell Physiol. 284, C2–15.

    PubMed  CAS  Google Scholar 

  • Verma, I.M., Stevenson, J.K., Schwarz, E.M., Van Antwerp, D., and Miyamoto, S. (1995). Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 9, 2723–2735.

    Article  PubMed  CAS  Google Scholar 

  • Votyakova, T.V., and Reynolds, I.J. (2001). DeltaPsi(m)-Dependent and -independent production of reactive oxygen species by rat brain mitochondria. J. Neurochem. 79, 266–277.

    Article  PubMed  CAS  Google Scholar 

  • Wajant, H., Pfizenmaier, K., and Scheurich, P. (2003). Tumor necrosis factor signaling. Cell Death Differ. 10, 45–65.

    Article  PubMed  CAS  Google Scholar 

  • Weisiger, R.A., and Fridovich, I. (1973a). Mitochondrial superoxide simutase. Site of synthesis and intramitochondrial localization. J. Biol. Chem. 248, 4793–4796.

    PubMed  CAS  Google Scholar 

  • Weisiger, R.A., and Fridovich, I. (1973b). Superoxide dismutase. Organelle specificity. J. Biol. Chem. 248, 3582–3592.

    CAS  Google Scholar 

  • Wilson, M.I., Gill, D.J., Perisic, O., Quinn, M.T., and Williams, R.L. (2003). PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62. Mol. Cell 12, 39–50.

    Article  PubMed  CAS  Google Scholar 

  • Wolter, K.G., Hsu, Y.T., Smith, C.L., Nechushtan, A., Xi, X.G., and Youle, R.J. (1997). Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139, 1281–1292.

    Article  PubMed  CAS  Google Scholar 

  • Wu, W.S. (2006). The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev. 25, 695–705.

    Article  PubMed  CAS  Google Scholar 

  • Yoo, Y.A., Kim, M.J., Park, J.K., Chung, Y.M., Lee, J.H., Chi, S.G., Kim, J.S., and Yoo, Y.D. (2005). Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1. Mol. Cell. Biol. 25, 6603–6616.

    Article  PubMed  CAS  Google Scholar 

  • Yuzawa, S., Ogura, K., Horiuchi, M., Suzuki, N.N., Fujioka, Y., Kataoka, M., Sumimoto, H., and Inagaki, F. (2004a). Solution structure of the tandem Src homology 3 domains of p47phox in an autoinhibited form. J. Biol. Chem. 279, 29752–29760.

    Article  PubMed  CAS  Google Scholar 

  • Yuzawa, S., Suzuki, N.N., Fujioka, Y., Ogura, K., Sumimoto, H., and Inagaki, F. (2004b). A molecular mechanism for autoinhibition of the tandem SH3 domains of p47phox, the regulatory subunit of the phagocyte NADPH oxidase. Genes Cells 9, 443–456.

    Article  PubMed  CAS  Google Scholar 

  • Zangar, R.C., Davydov, D.R., and Verma, S. (2004). Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol. Appl. Pharmacol. 199, 316–331.

    Article  PubMed  CAS  Google Scholar 

  • Zhuge, J., and Cederbaum, A.I. (2006). Serum deprivation-induced HepG2 cell death is potentiated by CYP2E1. Free Radic. Biol. Med. 40, 63–74.

    Article  PubMed  CAS  Google Scholar 

  • Zhukov, A.A., and Archakov, A.I. (1982). Complete stoichiometry of free NADPH oxidation in liver microsomes. Biochem. Biophys. Res. Commun. 109, 813–818.

    Article  PubMed  CAS  Google Scholar 

  • Zidi, I., Mestiri, S., Bartegi, A., and Amor, N.B. (2010). TNF-alpha and its inhibitors in cancer. Med. Oncol. 27, 185–198.

    Article  PubMed  CAS  Google Scholar 

  • Ziegler, G.A., Vonrhein, C., Hanukoglu, I., and Schulz, G.E. (1999). The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis. J. Mol. Biol. 289, 981–990.

    Article  PubMed  CAS  Google Scholar 

  • Zorov, D.B., Filburn, C.R., Klotz, L.O., Zweier, J.L., and Sollott, S.J. (2000). Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J. Exp. Med. 192, 1001–1014.

    Article  PubMed  CAS  Google Scholar 

  • Zorov, D.B., Juhaszova, M., and Sollott, S.J. (2006). Mitochondrial ROS-induced ROS release: an update and review. Biochim. Biophys. Acta 1757, 509–517.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Korea

    Yun Soo Bae & Sue Goo Rhee

  2. Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul, 136-705, Korea

    Young Do Yoo

Authors
  1. Yun Soo Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyunjin Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sue Goo Rhee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young Do Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yun Soo Bae, Sue Goo Rhee or Young Do Yoo.

About this article

Cite this article

Bae, Y.S., Oh, H., Rhee, S.G. et al. Regulation of reactive oxygen species generation in cell signaling. Mol Cells 32, 491–509 (2011). https://doi.org/10.1007/s10059-011-0276-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-011-0276-3

Keywords

Search

Navigation