O2 sensing, mitochondria and ROS signaling: The fog is lifting

Molecular Aspects of Medicine

Volumn 47-48, Issue , 2016, Pages 76-89

  Waypa, Gregory B ^a   Smith, Kimberly A ^a   Schumacker, Paul T ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

electron transport chain; Hypoxia; metabolism; oxidant signaling

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALCIUM CHANNEL L TYPE; CYTOCHROME C OXIDASE; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; STAT3 PROTEIN; SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIQUINOL CYTOCHROME C REDUCTASE; VOLTAGE GATED POTASSIUM CHANNEL; OXYGEN;

ARTICLE; CAROTID BODY CHEMORECEPTOR; CELL HYPOXIA; CITRIC ACID CYCLE; HUMAN; LIFESPAN; MEMBRANE DEPOLARIZATION; MITOCHONDRIAL ENERGY TRANSFER; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; NONHUMAN; OLFACTORY RECEPTOR; OXIDATION REDUCTION STATE; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; OXYGEN CONSUMPTION; OXYGEN SENSING; RESPIRATORY CHAIN; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; ANIMAL; BIOLOGICAL MODEL; DISEASE MODEL; HYPOXIA; METABOLISM; OXIDATION REDUCTION REACTION;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; HYPOXIA; MITOCHONDRIA; MODELS, BIOLOGICAL; OXIDATION-REDUCTION; OXYGEN; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 84958115349     PISSN: 00982997     EISSN: 18729452     Source Type: Journal    
DOI: 10.1016/j.mam.2016.01.002     Document Type: Review

References (148)

1. G. Ambrosio, J.L. Zweier, C. Duilio, P. Kuppusamy, G. Santoro, P.P. Elia, and et al. Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow J. Biol. Chem 268 25 1993 18532 18541
2. S. Archer, and E. Michelakis The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O(2) sensors, and controversies News Physiol. Sci 17 2002 131 137
3. S.L. Archer, D. Peterson, D.P. Nelson, E.G. DeMaster, B. Kelly, J.W. Eaton, and et al. Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung J. Appl. Physiol 66 1989 102 111
4. S.L. Archer, D.P. Nelson, and E.K. Weir Simultaneous measurement of O2 radicals and pulmonary vascular reactivity in rat lung J. Appl. Physiol. (1985) 67 5 1989 1903 1911
5. S.L. Archer, D.P. Nelson, and E.K. Weir Detection of activated O2 species in vitro and in rat lungs by chemiluminescence J. Appl. Physiol. (1985) 67 5 1989 1912 1921
6. 2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase Proc. Natl. Acad. Sci. U.S.A. 96 1999 7944 7949
7. S.L. Archer, E.D. Michelakis, B. Thebaud, S. Bonnet, R. Moudgil, Wu X.C., and et al. A central role for oxygen-sensitive K+ channels and mitochondria in the specialized oxygen-sensing system Novartis Found. Symp 272 2006 157 171
8. S.L. Archer, M. Gomberg-Maitland, M.L. Maitland, S. Rich, J.G. Garcia, and E.K. Weir Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer Am. J. Physiol. Heart Circ. Physiol 294 2 2008 H570 H578
9. D. Azevedo, F. Tacnet, A. Delaunay, C. Rodrigues-Pousada, and M.B. Toledano Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling Free Radic. Biol. Med 35 8 2003 889 900
10. Y.S. Bae, H. Oh, S.G. Rhee, and Y.D. Yoo Regulation of reactive oxygen species generation in cell signaling Mol. Cells 32 6 2011 491 509
11. R. Baradaran, J.M. Berrisford, G.S. Minhas, and L.A. Sazanov Crystal structure of the entire respiratory complex I Nature 494 7438 2013 443 448
12. L.B. Becker, T.L. Vanden Hoek, Shao Z.H., Li C.Q., and P.T. Schumacker Generation of superoxide in cardiomyocytes during ischemia before reperfusion Am. J. Physiol 277 6 Pt 2 1999 H2240 H2246
13. E.L. Bell, T.A. Klimova, J. Eisenbart, P.T. Schumacker, and N.S. Chandel Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia Mol. Cell. Biol 27 16 2007 5737 5745
14. S.K. Berkelhamer, G.A. Kim, J.E. Radder, S. Wedgwood, L. Czech, R.H. Steinhorn, and et al. Developmental differences in hyperoxia-induced oxidative stress and cellular responses in the murine lung Free Radic. Biol. Med 61 2013 51 60
15. S. Bonnet, and S.L. Archer Potassium channel diversity in the pulmonary arteries and pulmonary veins: implications for regulation of the pulmonary vasculature in health and during pulmonary hypertension Pharmacol. Ther 115 1 2007 56 69
16. A. Boveris, and E. Cadenas Mitochondrial production of hydrogen peroxide regulation by nitric oxide and the role of ubisemiquinone IUBMB Life 50 4-5 2000 245 250
17. A. Boveris, N. Oshino, and B. Chance The cellular production of hydrogen peroxide Biochem. J. 128 3 1972 617 630
18. R. Brigelius-Flohe, and L. Flohe Basic principles and emerging concepts in the redox control of transcription factors Antioxid. Redox Signal 15 8 2011 2335 2381
19. K.J. Buckler, and P.J. Turner Oxygen sensitivity of mitochondrial function in rat arterial chemoreceptor cells J. Physiol 591 Pt 14 2013 3549 3563
20. D.G. Buerk, P.K. Nair, and W.J. Whalen Two-cytochrome metabolic model for carotid body PtiO2 and chemosensitivity changes after hemorrhage J. Appl. Physiol 67 1 1989 60 68
21. D.G. Buerk, P.K. Nair, and W.J. Whalen Evidence for second metabolic pathway for O2 from PtiO2 measurements in denervated cat carotid body J. Appl. Physiol 67 4 1989 1578 1584
22. P. Carmeliet, Y. Dor, J.M. Herbert, D. Fukumura, K. Brusselmans, M. Dewerchin, and et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis Nature 394 6692 1998 485 490
23. N.S. Chandel, and P.T. Schumacker Cellular oxygen sensing by mitochondria: old questions, new insight J. Appl. Physiol 88 5 2000 1880 1889
24. N.S. Chandel, G.R.S. Budinger, S.H. Choe, and P.T. Schumacker Cellular respiration during hypoxia: role of cytochrome oxidase as the oxygen sensor in hepatocytes J. Biol. Chem 272 1 1997 111 112
25. N.S. Chandel, E. Maltepe, E. Goldwasser, C.E. Mathieu, M.C. Simon, and P.T. Schumacker Mitochondrial reactive oxygen species trigger hypoxia-induced transcription Proc. Natl. Acad. Sci. U.S.A. 95 1998 11715 11720
26. N.S. Chandel, W.C. Trzyna, D.S. McClintock, and P.T. Schumacker Role of oxidants in NF-kappaB activation and TNF-alpha gene transcription induced by hypoxia and endotoxin J. Immunol 165 2 2000 1013 1021
27. N.S. Chandel, D.S. McClintock, C.E. Feliciano, T.M. Wood, J.A. Melendez, A.M. Rodriguez, and et al. Reactive oxygen species generated at mitochondrial Complex III stabilize HIF-1-alpha during hypoxia: a mechanism of O2 sensing J. Biol. Chem 275 2000 25130 25138
28. Chang A.J., F.E. Ortega, J. Riegler, D.V. Madison, and M.A. Krasnow Oxygen regulation of breathing through an olfactory receptor activated by lactate Nature 527 7577 2015 240 244
29. Chang J., H.J. Jung, S.H. Jeong, H.K. Kim, Han J., and H.J. Kwon A mutation in the mitochondrial protein UQCRB promotes angiogenesis through the generation of mitochondrial reactive oxygen species Biochem. Biophys. Res. Commun 455 3-4 2014 290 297
30. Y.S. Cho, H.J. Jung, S.H. Seok, A.Y. Payumo, Chen J.K., and H.J. Kwon Functional inhibition of UQCRB suppresses angiogenesis in zebrafish Biochem. Biophys. Res. Commun 433 4 2013 396 400
31. C.E. Cross, B. Halliwell, E.T. Borish, W.A. Pryor, B.N. Ames, R.L. Saul, and et al. Oxygen radicals and human disease Ann. Intern. Med 107 1987 526 545
32. A. Delaunay, D. Pflieger, M.B. Barrault, J. Vinh, and M.B. Toledano A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation Cell 111 4 2002 471 481
33. F. Di Lisa, R. Menabo, M. Canton, and V. Petronilli The role of mitochondria in the salvage and the injury of the ischemic myocardium Biochim. Biophys. Acta 1366 1-2 1998 69 78
34. C.T. Dooley, T.M. Dore, G.T. Hanson, W.C. Jackson, S.J. Remington, and R.Y. Tsien Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators J. Biol. Chem 279 21 2004 22284 22293
35. K.J. Dunham-Snary, Hong Z.G., Xiong P.Y., J.C. Del Paggio, J.E. Herr, A.M. Johri, and et al. A mitochondrial redox oxygen sensor in the pulmonary vasculature and ductus arteriosus Pflugers Arch 468 1 2016 43 58
36. J. Duranteau, N.S. Chandel, A. Kulisz, Shao Z., and P.T. Schumacker Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes J. Biol. Chem 273 19 1998 11619 11624
37. K.N. Farrow, K.J. Lee, M. Perez, J.M. Schriewer, S. Wedgwood, S. Lakshminrusimha, and et al. Brief hyperoxia increases mitochondrial oxidation and increases phosphodiesterase 5 activity in fetal pulmonary artery smooth muscle cells Antioxid. Redox Signal 17 3 2012 460 470
38. M.C. Fernandez-Aguera, Gao L., P. Gonzalez-Rodriguez, C.O. Pintado, I. Rias-Mayenco, P. Garcia-Flores, and et al. Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling Cell Metab 22 5 2015 825 837
39. R. Ferrari The role of mitochondria in ischemic heart disease J. Cardiovasc. Pharmacol 28 Suppl. 1 1996 S1 S10
40. T. Finkel Signal transduction by mitochondrial oxidants J. Biol. Chem 287 7 2012 4434 4440
41. B.A. Freeman, and J.D. Crapo Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria J. Biol. Chem 256 21 1981 10986 10992
42. B. Fuchs, N. Sommer, A. Dietrich, R.T. Schermuly, H.A. Ghofrani, F. Grimminger, and et al. Redox signaling and reactive oxygen species in hypoxic pulmonary vasoconstriction Respir. Physiol. Neurobiol 174 3 2010 282 291
43. C. Garcia-Ruiz, A. Colell, A. Morales, N. Kaplowitz, and J.C. Fernandez-Checa Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes Mol. Pharmacol 48 5 1995 825 834
44. C. Garcia-Ruiz, A. Colell, M. Mari, A. Morales, and J.C. Fernandez-Checa Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione J. Biol. Chem 272 17 1997 11369 11377
45. M.L. Genova, B. Ventura, G. Giuliano, C. Bovina, G. Formiggini, G.P. Castelli, and et al. The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2 FEBS Lett 505 3 2001 364 368
46. L. Gille, and H. Nohl The ubiquinol/bc1 redox couple regulates mitochondrial oxygen radical formation Arch. Biochem. Biophys 388 1 2001 34 38
47. M.N. Gillespie, V.M. Pastukh, and M.V. Ruchko Controlled DNA "damage" and repair in hypoxic signaling Respir. Physiol. Neurobiol 174 3 2010 244 251
48. R.D. Guzy, B. Hoyos, E. Robin, Chen H., Liu L., K.D. Mansfield, and et al. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing Cell Metab 1 6 2005 401 408
49. R.D. Guzy, M.M. Mack, and P.T. Schumacker Mitochondrial complex III is required for hypoxia-induced ROS production and gene transcription in yeast Antioxid. Redox Signal 9 9 2007 1317 1328
50. T. Hagen, C.T. Taylor, F. Lam, and S. Moncada Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha Science 302 5652 2003 1975 1978
51. G.T. Hanson, R. Aggeler, D. Oglesbee, M. Cannon, R.A. Capaldi, R.Y. Tsien, and et al. Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators J. Biol. Chem 279 13 2004 13044 13053
52. S. Haut, M. Brivet, G. Touati, P. Rustin, S. Lebon, A. Garcia-Cazorla, and et al. A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis Hum. Genet 113 2 2003 118 122
53. M.C. Hogan Phosphorescence quenching method for measurement of intracellular Po2 in isolated skeletal muscle fibers J. Appl. Physiol 86 2 1999 720 724
54. 2-dependent degradation domain via the ubiquitin-proteasome pathway Proc. Natl. Acad. Sci. U.S.A. 95 14 1998 7987 7992
55. M. Ivan, K. Kondo, Yang H., W. Kim, J. Valiando, M. Ohh, and et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing Science 292 5516 2001 464 468
56. N.V. Iyer, L.E. Kotch, F. Agani, S.W. Leung, E. Laughner, R.H. Wenger, and et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha Genes Dev 12 2 1998 149 162
57. P. Jaakkola, D.R. Mole, Tian Y.M., M.I. Wilson, J. Gielbert, S.J. Gaskell, and et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation Science 292 5516 2001 468 472
58. P.K. Jensen Antimycin-insensitive oxidation of succinate and reduced nicotinamide-adenine dinucleotide in electron-tranport particles Biochim. Biophys. Acta 122 1966 157 166
59. 2 tension Am. J. Physiol 271 4 Pt 1 1996 C1172 C1180
60. H.J. Jung, J.S. Shim, J. Lee, Song Y.M., K.C. Park, S.H. Choi, and et al. Terpestacin inhibits tumor angiogenesis by targeting UQCRB of mitochondrial complex III and suppressing hypoxia-induced reactive oxygen species production and cellular oxygen sensing J. Biol. Chem 285 15 2010 11584 11595
61. W.G. Kaelin Jr., and P.J. Ratcliffe Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway Mol. Cell 30 4 2008 393 402
62. Y.E. Koo, Cao Y., R. Kopelman, S.M. Koo, M. Brasuel, and M.A. Philbert Real-time measurements of dissolved oxygen inside live cells by organically modified silicate fluorescent nanosensors Anal. Chem 76 9 2004 2498 2505
63. L.K. Kwong, and R.S. Sohal Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria Arch. Biochem. Biophys 350 1998 118 126
64. D. Lando, D.J. Peet, D.A. Whelan, J.J. Gorman, and M.L. Whitelaw Asparagine hydroxylation of the HIF transactivation domain: a hypoxic switch Science 295 5556 2002 858 861
65. D. Lando, D.J. Peet, J.J. Gorman, D.A. Whelan, M.L. Whitelaw, and R.K. Bruick FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor Genes Dev 16 12 2002 1466 1471
66. G. Lebuffe, P.T. Schumacker, Shao Z.H., T. Anderson, H. Iwase, and T.L. Vanden Hoek ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel Am. J. Physiol. Heart Circ. Physiol 284 1 2003 H299 H308
67. S.J. Lee, A.B. Hwang, and C. Kenyon Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity Curr. Biol 20 23 2010 2131 2136
68. Li S., S.S. Tabar, V. Malec, B.G. Eul, W. Klepetko, N. Weissmann, and et al. NOX4 regulates ROS levels under normoxic and hypoxic conditions, triggers proliferation, and inhibits apoptosis in pulmonary artery adventitial fibroblasts Antioxid. Redox Signal 10 10 2008 1687 1698
69. Li Y., and M.A. Trush Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production Biochem. Biophys. Res. Commun 253 2 1998 295 299
70. Liu H.J., R. Colavitti, I.I. Rovira, and T. Finkel Redox-dependent transcriptional regulation Circ. Res 97 10 2005 967 974
71. E. Maltepe, and M.C. Simon Oxygen, genes, and development: an analysis of the role of hypoxic gene regulation during murine vascular development J. Mol. Med 76 6 1998 391 401
72. E. Maltepe, J.V. Schmidt, D. Baunoch, C.A. Bradfield, and M.C. Simon Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT Nature 386 6623 1997 403 407
73. K.D. Mansfield, R.D. Guzy, Pan Y., R.M. Young, T.P. Cash, P.T. Schumacker, and et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation Cell Metab 1 6 2005 393 399
74. C. Marshall, A.J. Mamary, A.J. Verhoeven, and B.E. Marshall Pulmonary artery NADPH-oxidase is activated in hypoxic pulmonary vasoconstriction Am. J. Respir. Cell. Mol. Biol 15 1996 633 644
75. N. Masson, R.S. Singleton, R. Sekirnik, D.C. Trudgian, L.J. Ambrose, M.X. Miranda, and et al. The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity EMBO Rep 13 3 2012 251 257
76. P.H. Maxwell, M.S. Wiesener, Chang G.W., S.C. Clifford, E.C. Vaux, M.E. Cockman, and et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis Nature 399 6733 1999 271 275
77. J.M. McCord Oxygen-derived free radicals in postischemic tissue injury N. Engl. J. Med 3 1985 159 163
78. R. Mehta, K.A. Steinkraus, G.L. Sutphin, F.J. Ramos, L.S. Shamieh, A. Huh, and et al. Proteasomal regulation of the hypoxic response modulates aging in C. elegans Science 324 5931 2009 1196 1198
79. E.D. Michelakis, S.L. Archer, and E.K. Weir Acute hypoxic pulmonary vasoconstriction: a model of oxygen sensing Physiol. Res 44 6 1995 361 367
80. E.D. Michelakis, V. Hampl, A. Nsair, Wu X.C., G. Harry, A. Haromy, and et al. Diversity in mitochondrial function explains differences in vascular oxygen sensing Circ. Res 90 12 2002 1307 1315
81. E.D. Michelakis, I. Rebeyka, Wu X., A. Nsair, B. Thebaud, K. Hashimoto, and et al. O2 sensing in the human ductus arteriosus: regulation of voltage-gated K+ channels in smooth muscle cells by a mitochondrial redox sensor Circ. Res 91 6 2002 478 486
82. E.G. Mik, J. Stap, M. Sinaasappel, J.F. Beek, J.A. Aten, T.G. van Leeuwen, and et al. Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX Nat. Methods 3 11 2006 939 945
83. E. Mills, and F.F. Jobsis Mitochondrial respiratory chain of carotid body and chemoreceptor response to changes in oxygen tension J. Neurophysiol 35 4 1972 405 428
84. H.P. Misra, and I. Fridovich The univalent reduction of oxygen by reduced flavins and quinones J. Biol. Chem 247 1972 188 192
85. D.R. Mole, P.H. Maxwell, C.W. Pugh, and P.J. Ratcliffe Regulation of HIF by the von Hippel-Lindau tumour suppressor: implications for cellular oxygen sensing IUBMB Life 52 1-2 2001 43 47
86. R. Moudgil, E.D. Michelakis, and S.L. Archer The role of k+ channels in determining pulmonary vascular tone, oxygen sensing, cell proliferation, and apoptosis: implications in hypoxic pulmonary vasoconstriction and pulmonary arterial hypertension Microcirculation 13 8 2006 615 632
87. P.T. Mungai, G.B. Waypa, A. Jairaman, M. Prakriya, D. Dokic, M.K. Ball, and et al. Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels Mol. Cell. Biol 31 17 2011 3531 3545
88. M.P. Murphy How mitochondria produce reactive oxygen species Biochem. J. 417 1 2009 1 13
89. M.P. Murphy, A. Holmgren, N.G. Larsson, B. Halliwell, Chang C.J., B. Kalyanaraman, and et al. Unraveling the biological roles of reactive oxygen species Cell Metab 13 4 2011 361 366
90. P.K. Nair, D.G. Buerk, W.J. Whalen, and R.W. Schubert Two cytochrome oxygen consumption model and mechanism for carotid body chemoreception Adv. Exp. Med. Biol 200 1986 293 300
91. A.L. Orr, D. Ashok, M.R. Sarantos, Shi T., R.E. Hughes, and M.D. Brand Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening Free Radic. Biol. Med 65 2013 1047 1059
92. A.L. Orr, L. Vargas, C.N. Turk, J.E. Baaten, J.T. Matzen, V.J. Dardov, and et al. Suppressors of superoxide production from mitochondrial complex III Nat. Chem. Biol 11 11 2015 834 836
93. P. Ortega-Saenz, R. Pardal, M.G. Fernandez, and J. Lopez-Barneo Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells J. Physiol 548 3 2003 789 800
94. A. Paky, J.R. Michael, T.M. Burke-Wolin, M.S. Wolin, and G.H. Gurtner Endogenous production of superoxide by rabbit lungs: effects of hypoxia or metabolic inhibitors J. Appl. Physiol 74 6 1993 2868 2874
95. D.P. Pearlstein, M.H. Ali, P.T. Mungai, K.L. Hynes, B.L. Gewertz, and P.T. Schumacker Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia Arterioscler. Thromb. Vasc. Biol 22 4 2002 566 573
96. A. Quillet-Mary, J.P. Jaffrezou, V. Mansat, C. Bordier, J. Naval, and G. Laurent Implication of mitochondrial hydrogen peroxide generation in ceramide-induced apoptosis J. Biol. Chem 272 34 1997 21388 21395
97. C.L. Quinlan, I.V. Perevoshchikova, M. Hey-Mogensen, A.L. Orr, and M.D. Brand Sites of reactive oxygen species generation by mitochondria oxidizing different substrates Redox Biol 1 2013 304 312
98. R. Rathore, Zheng Y.M., Li X.Q., Wang Q.S., Liu Q.H., R. Ginnan, and et al. Mitochondrial ROS-PKCepsilon signaling axis is uniquely involved in hypoxic increase in [Ca2+]i in pulmonary artery smooth muscle cells Biochem. Biophys. Res. Commun 351 3 2006 784 790
99. H.L. Reeve, E.K. Weir, D.P. Nelson, D.A. Peterson, and S.L. Archer Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue Exp. Physiol 80 5 1995 825 834
100. H.L. Reeve, S. Tolarova, D.P. Nelson, S. Archer, and E.K. Weir Redox control of oxygen sensing in the rabbit ductus arteriosus J. Physiol 533 1 2001 253 261
101. S.J. Remington Fluorescent proteins: maturation, photochemistry and photophysics Curr. Opin. Struct. Biol 16 6 2006 714 721
102. S.G. Rhee, H.A. Woo, I.S. Kil, and S.H. Bae Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides J. Biol. Chem 287 7 2012 4403 4410
103. W.L. Rumsey, C. Schlosser, E.M. Nuutinen, M. Robiolio, and D.F. Wilson Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat J. Biol. Chem 265 1990 15392 15399
104. L.K. Russell, B.N. Finck, and D.P. Kelly Mouse models of mitochondrial dysfunction and heart failure J. Mol. Cell. Cardiol 38 1 2005 81 91
105. S.S. Sabharwal, and P.T. Schumacker Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel? Nat. Rev. Cancer 14 11 2014 709 721
106. S.S. Sabharwal, G.B. Waypa, J.D. Marks, and P.T. Schumacker Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling Biochem. J. 456 3 2013 337 346
107. A. Sanjuan-Pla, A.M. Cervera, N. Apostolova, R. Garcia-Bou, V.M. Victor, M.P. Murphy, and et al. A targeted antioxidant reveals the importance of mitochondrial reactive oxygen species in the hypoxic signaling of HIF-1alpha FEBS Lett 579 12 2005 2669 2674
108. A.H. Schapira Human complex I defects in neurodegenerative diseases Biochim. Biophys. Acta 1364 2 1998 261 270
109. M. Schieber, and N.S. Chandel TOR signaling couples oxygen sensing to lifespan in C. elegans Cell Rep 9 1 2014 9 15
110. 2 sensing E.R. Swensen, P. Bärtsch, High Altitude: Human Adaptation to Hypoxia first ed. 2014 Springer New York 1 22
111. J.S. Scotti, I.K. Leung, Ge W., M.A. Bentley, J. Paps, H.B. Kramer, and et al. Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation Proc. Natl. Acad. Sci. U.S.A. 111 37 2014 13331 13336
112. G.L. Semenza HIF-1, O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus Cell 107 1 2001 1 3
113. G.L. Semenza Oxygen homeostasis Wiley Interdiscip. Rev. Syst. Biol. Med 2 3 2010 336 361
114. G.L. Semenza Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics Oncogene 29 5 2010 625 634
115. L.A. Sena, and N.S. Chandel Physiological roles of mitochondrial reactive oxygen species Mol. Cell 48 2 2012 158 167
116. H. Shimada, K. Hirai, E. Simamura, and Pan J. Mitochondrial NADH-quinone oxidoreductase of the outer membrane is responsible for paraquat cytotoxicity in rat livers Arch. Biochem. Biophys 351 1 1998 75 81
117. L.A. Shimoda, and G.L. Semenza HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease Am. J. Respir. Crit. Care Med 183 2 2011 152 156
118. Song D., Li L.S., K.J. Heaton-Johnson, P.R. Arsenault, S.R. Master, and F.S. Lee Prolyl hydroxylase domain protein 2 (PHD2) binds a Pro-Xaa-Leu-Glu motif, linking it to the heat shock protein 90 pathway J. Biol. Chem 288 14 2013 9662 9674
119. K. Takeda, V.C. Ho, H. Takeda, Duan L.J., A. Nagy, and G.H. Fong Placental but not heart defects are associated with elevated hypoxia-inducible factor alpha levels in mice lacking prolyl hydroxylase domain protein Mol. Cell. Biol 26 22 2006 8336 8346
120. H. Tarhonskaya, A.P. Hardy, E.A. Howe, N.D. Loik, H.B. Kramer, J.S. McCullagh, and et al. Kinetic investigations of the role of factor inhibiting hypoxia-inducible factor (FIH) as an oxygen sensor J. Biol. Chem 290 32 2015 19726 19742
121. V.J. Thannickal Oxygen in the evolution of complex life and the price we pay Am. J. Respir. Cell Mol. Biol 40 5 2009 507 510
122. Tian Y.M., K.K. Yeoh, M.K. Lee, T. Eriksson, B.M. Kessler, H.B. Kramer, and et al. Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitors J. Biol. Chem 286 15 2011 13041 13051
123. J.F. Turrens, and A. Boveris Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria Biochem. J. 191 1980 421 427
124. J.F. Turrens, A. Alexandre, and A.L. Lehninger Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria Arch. Biochem. Biophys 237 1985 408 414
125. J.F. Turrens, M. Beconi, J. Barilla, U.B. Chavez, and J.M. McCord Mitochondrial generation of oxygen radicals during reoxygenation of ischemic tissues Free Radic. Res. Commun 12-13 Pt 2 1991 681 689
126. T.L. Vanden Hoek, Li C., Shao Z., P.T. Schumacker, and L.B. Becker Significant levels of oxidants are generated by isolated cardiomyocytes during ischemia prior to reperfusion J. Mol. Cell. Cardiol 29 1997 2571 2583
127. T.L. Vanden Hoek, L.B. Becker, Shao Z., Li C., and P.T. Schumacker Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes J. Biol. Chem 273 1998 18092 18098
128. E.C. Vaux, E. Metzen, K.M. Yeates, and P.J. Ratcliffe Regulation of hypoxia-inducible factor is preserved in the absence of a functioning mitochondrial respiratory chain Blood 98 2 2001 296 302
129. T.V. Votyakova, and I.J. Reynolds DeltaPsi(m)-Dependent and -independent production of reactive oxygen species by rat brain mitochondria J. Neurochem 79 2 2001 266 277
130. 2 tension Proc. Natl. Acad. Sci. U.S.A. 92 1995 5510 5514
131. Wang Q.S., Zheng Y.M., Dong L., Y.S. Ho, Guo Z., and Wang Y.X. Role of mitochondrial reactive oxygen species in hypoxia-dependent increase in intracellular calcium in pulmonary artery myocytes Free Radic. Biol. Med 42 5 2007 642 653
132. Wang Y.X., and Zheng Y.M. Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells Respir. Physiol. Neurobiol 174 3 2010 192 200
133. G.B. Waypa, N.S. Chandel, and P.T. Schumacker Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing Circ. Res 88 12 2001 1259 1266
134. G.B. Waypa, J.D. Marks, M.M. Mack, C. Boriboun, P.T. Mungai, and P.T. Schumacker Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes Circ. Res 91 8 2002 719 726
135. G.B. Waypa, R. Guzy, P.T. Mungai, M.M. Mack, J.D. Marks, M.W. Roe, and et al. Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells Circ. Res 99 9 2006 970 978
136. G.B. Waypa, J.D. Marks, R. Guzy, P.T. Mungai, J. Schriewer, D. Dokic, and et al. Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells Circ. Res 106 3 2010 526 535
137. G.B. Waypa, J.D. Marks, R. Guzy, P.T. Mungai, J. Schriewer, D. Dokic, and et al. Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells Circ. Res 106 3 2010 526 535
138. G.B. Waypa, J.D. Marks, R.D. Guzy, P.T. Mungai, J.M. Schriewer, D. Dokic, and et al. Superoxide generated at mitochondrial complex III triggers acute responses to hypoxia in the pulmonary circulation Am. J. Respir. Crit. Care Med 187 4 2013 424 432
139. E.K. Weir, and S.L. Archer The mechanism of acute hypoxic pulmonary vasoconstriction: a tale of two channels FASEB J. 9 1995 183 189
140. E.K. Weir, and S.L. Archer The role of redox changes in oxygen sensing Respir. Physiol. Neurobiol 174 3 2010 182 191
141. E.K. Weir, H.L. Reeve, D.A. Peterson, E.D. Michelakis, D.P. Nelson, and S.L. Archer Pulmonary vasoconstriction, oxygen sensing, and the role of ion channels - Thomas A. Neff Lecture Chest 114 1 1998 17S 22S
142. E.K. Weir, J. Lopez-Barneo, K.J. Buckler, and S.L. Archer Mechanisms of disease - Acute oxygen-sensing mechanisms N. Engl. J. Med 353 19 2005 2042 2055
143. S.M. Welford, B. Bedogni, K. Gradin, L. Poellinger, P.M. Broome, and A.J. Giaccia HIF1alpha delays premature senescence through the activation of MIF Genes Dev 20 24 2006 3366 3371
144. D.F. Wilson Contribution of diffusion to the oxygen dependence of energy metabolism in cells Experientia 46 1990 1160 1162
145. D.F. Wilson, W.L. Rumsey, T.J. Green, and J.M. Vanderkooi The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration J. Biol. Chem 263 1988 2712 2718
146. D.F. Wilson, A. Mokashi, D. Chugh, S. Vinogradov, S. Osanai, and S. Lahiri The primary oxygen sensor of the cat carotid body is cytochrome a3 of the mitochondrial respiratory chain FEBS Lett 351 3 1994 370 374
147. Zhang L., Yu L.D., and Yu C.A. Generation of superoxide anion by succinate-cytochrome c reductase from bovine heart mitochondria J. Biol. Chem 273 51 1998 33972 33976
148. Zhao J.P., Zhou Z.G., Hu H.L., Guo Z., Wang T., Zhen G.H., and et al. The relationships among reactive oxygen species, hypoxia-inducible factor 1alpha and cell proliferation in rat pulmonary arterial smooth muscle cells under hypoxia Sheng Li Xue Bao 59 3 2007 319 324