O 2 sensing, mitochondria and ROS signaling: The fog is lifting

Ambrosio, 1993, 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, 18532, 10.1016/S0021-9258(17)46660-9 Archer, 2002, The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O(2) sensors, and controversies, News Physiol. Sci, 17, 131 Archer, 1989, Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung, J. Appl. Physiol, 66, 102, 10.1152/jappl.1989.66.1.102 Archer, 1989, Simultaneous measurement of O2 radicals and pulmonary vascular reactivity in rat lung, J. Appl. Physiol. (1985), 67, 1903, 10.1152/jappl.1989.67.5.1903 Archer, 1989, Detection of activated O2 species in vitro and in rat lungs by chemiluminescence, J. Appl. Physiol. (1985), 67, 1912, 10.1152/jappl.1989.67.5.1912 Archer, 1999, O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase, Proc. Natl. Acad. Sci. U.S.A., 96, 7944, 10.1073/pnas.96.14.7944 Archer, 2006, A central role for oxygen-sensitive K+ channels and mitochondria in the specialized oxygen-sensing system, Novartis Found. Symp, 272, 157, 10.1002/9780470035009.ch13 Archer, 2008, 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, H570, 10.1152/ajpheart.01324.2007 Azevedo, 2003, Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling, Free Radic. Biol. Med, 35, 889, 10.1016/S0891-5849(03)00434-9 Bae, 2011, Regulation of reactive oxygen species generation in cell signaling, Mol. Cells, 32, 491, 10.1007/s10059-011-0276-3 Baradaran, 2013, Crystal structure of the entire respiratory complex I, Nature, 494, 443, 10.1038/nature11871 Becker, 1999, Generation of superoxide in cardiomyocytes during ischemia before reperfusion, Am. J. Physiol, 277, H2240 Bell, 2007, Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia, Mol. Cell. Biol, 27, 5737, 10.1128/MCB.02265-06 Berkelhamer, 2013, Developmental differences in hyperoxia-induced oxidative stress and cellular responses in the murine lung, Free Radic. Biol. Med, 61, 51, 10.1016/j.freeradbiomed.2013.03.003 Bonnet, 2007, 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, 56, 10.1016/j.pharmthera.2007.03.014 Boveris, 2000, Mitochondrial production of hydrogen peroxide regulation by nitric oxide and the role of ubisemiquinone, IUBMB Life, 50, 245, 10.1080/15216540051080912 Boveris, 1972, The cellular production of hydrogen peroxide, Biochem. J., 128, 617, 10.1042/bj1280617 Brigelius-Flohe, 2011, Basic principles and emerging concepts in the redox control of transcription factors, Antioxid. Redox Signal, 15, 2335, 10.1089/ars.2010.3534 Buckler, 2013, Oxygen sensitivity of mitochondrial function in rat arterial chemoreceptor cells, J. Physiol, 591, 3549, 10.1113/jphysiol.2013.257741 Buerk, 1989, Two-cytochrome metabolic model for carotid body PtiO2 and chemosensitivity changes after hemorrhage, J. Appl. Physiol, 67, 60, 10.1152/jappl.1989.67.1.60 Buerk, 1989, Evidence for second metabolic pathway for O2 from PtiO2 measurements in denervated cat carotid body, J. Appl. Physiol, 67, 1578, 10.1152/jappl.1989.67.4.1578 Carmeliet, 1998, Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis, Nature, 394, 485, 10.1038/28867 Chandel, 2000, Cellular oxygen sensing by mitochondria: old questions, new insight, J. Appl. Physiol, 88, 1880, 10.1152/jappl.2000.88.5.1880 Chandel, 1997, Cellular respiration during hypoxia: role of cytochrome oxidase as the oxygen sensor in hepatocytes, J. Biol. Chem, 272, 111 Chandel, 1998, Mitochondrial reactive oxygen species trigger hypoxia-induced transcription, Proc. Natl. Acad. Sci. U.S.A., 95, 11715, 10.1073/pnas.95.20.11715 Chandel, 2000, Role of oxidants in NF-kappaB activation and TNF-alpha gene transcription induced by hypoxia and endotoxin, J. Immunol, 165, 1013, 10.4049/jimmunol.165.2.1013 Chandel, 2000, Reactive oxygen species generated at mitochondrial Complex III stabilize HIF-1-alpha during hypoxia: a mechanism of O2 sensing, J. Biol. Chem, 275, 25130, 10.1074/jbc.M001914200 Chang, 2015, Oxygen regulation of breathing through an olfactory receptor activated by lactate, Nature, 527, 240, 10.1038/nature15721 Chang, 2014, A mutation in the mitochondrial protein UQCRB promotes angiogenesis through the generation of mitochondrial reactive oxygen species, Biochem. Biophys. Res. Commun, 455, 290, 10.1016/j.bbrc.2014.11.005 Cho, 2013, Functional inhibition of UQCRB suppresses angiogenesis in zebrafish, Biochem. Biophys. Res. Commun, 433, 396, 10.1016/j.bbrc.2013.02.082 Cross, 1987, Oxygen radicals and human disease, Ann. Intern. Med, 107, 526, 10.7326/0003-4819-107-4-526 Delaunay, 2002, A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation, Cell, 111, 471, 10.1016/S0092-8674(02)01048-6 Di Lisa, 1998, The role of mitochondria in the salvage and the injury of the ischemic myocardium, Biochim. Biophys. Acta, 1366, 69, 10.1016/S0005-2728(98)00121-2 Dooley, 2004, Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators, J. Biol. Chem, 279, 22284, 10.1074/jbc.M312847200 Dunham-Snary, 2016, A mitochondrial redox oxygen sensor in the pulmonary vasculature and ductus arteriosus, Pflugers Arch, 468, 43, 10.1007/s00424-015-1736-y Duranteau, 1998, Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes, J. Biol. Chem, 273, 11619, 10.1074/jbc.273.19.11619 Farrow, 2012, Brief hyperoxia increases mitochondrial oxidation and increases phosphodiesterase 5 activity in fetal pulmonary artery smooth muscle cells, Antioxid. Redox Signal, 17, 460, 10.1089/ars.2011.4184 Fernandez-Aguera, 2015, Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling, Cell Metab, 22, 825, 10.1016/j.cmet.2015.09.004 Ferrari, 1996, The role of mitochondria in ischemic heart disease, J. Cardiovasc. Pharmacol, 28, S1 Finkel, 2012, Signal transduction by mitochondrial oxidants, J. Biol. Chem, 287, 4434, 10.1074/jbc.R111.271999 Freeman, 1981, Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria, J. Biol. Chem, 256, 10986, 10.1016/S0021-9258(19)68544-3 Fuchs, 2010, Redox signaling and reactive oxygen species in hypoxic pulmonary vasoconstriction, Respir. Physiol. Neurobiol, 174, 282, 10.1016/j.resp.2010.08.013 Garcia-Ruiz, 1995, Mol. Pharmacol, 48, 825 Garcia-Ruiz, 1997, 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, 11369, 10.1074/jbc.272.17.11369 Genova, 2001, 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, 364, 10.1016/S0014-5793(01)02850-2 Gille, 2001, The ubiquinol/bc1 redox couple regulates mitochondrial oxygen radical formation, Arch. Biochem. Biophys, 388, 34, 10.1006/abbi.2000.2257 Gillespie, 2010, Controlled DNA “damage” and repair in hypoxic signaling, Respir. Physiol. Neurobiol, 174, 244, 10.1016/j.resp.2010.08.025 Guzy, 2005, Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing, Cell Metab, 1, 401, 10.1016/j.cmet.2005.05.001 Guzy, 2007, Mitochondrial complex III is required for hypoxia-induced ROS production and gene transcription in yeast, Antioxid. Redox Signal, 9, 1317, 10.1089/ars.2007.1708 Hagen, 2003, Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha, Science, 302, 1975, 10.1126/science.1088805 Hanson, 2004, Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators, J. Biol. Chem, 279, 13044, 10.1074/jbc.M312846200 Haut, 2003, A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis, Hum. Genet, 113, 118, 10.1007/s00439-003-0946-0 Hogan, 1999, Phosphorescence quenching method for measurement of intracellular Po2 in isolated skeletal muscle fibers, J. Appl. Physiol, 86, 720, 10.1152/jappl.1999.86.2.720 Huang, 1998, Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway, Proc. Natl. Acad. Sci. U.S.A., 95, 7987, 10.1073/pnas.95.14.7987 Ivan, 2001, HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing, Science, 292, 464, 10.1126/science.1059817 Iyer, 1998, Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha, Genes Dev, 12, 149, 10.1101/gad.12.2.149 Jaakkola, 2001, Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation, Science, 292, 468, 10.1126/science.1059796 Jensen, 1966, Antimycin-insensitive oxidation of succinate and reduced nicotinamide-adenine dinucleotide in electron-tranport particles, Biochim. Biophys. Acta, 122, 157, 10.1016/0926-6593(66)90057-9 Jiang, 1996, Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension, Am. J. Physiol, 271, C1172, 10.1152/ajpcell.1996.271.4.C1172 Jung, 2010, 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, 11584, 10.1074/jbc.M109.087809 Kaelin, 2008, Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway, Mol. Cell, 30, 393, 10.1016/j.molcel.2008.04.009 Koo, 2004, Real-time measurements of dissolved oxygen inside live cells by organically modified silicate fluorescent nanosensors, Anal. Chem, 76, 2498, 10.1021/ac035493f Kwong, 1998, Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria, Arch. Biochem. Biophys, 350, 118, 10.1006/abbi.1997.0489 Lando, 2002, Asparagine hydroxylation of the HIF transactivation domain: a hypoxic switch, Science, 295, 858, 10.1126/science.1068592 Lando, 2002, FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor, Genes Dev, 16, 1466, 10.1101/gad.991402 Lebuffe, 2003, ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel, Am. J. Physiol. Heart Circ. Physiol, 284, H299, 10.1152/ajpheart.00706.2002 Lee, 2010, Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity, Curr. Biol, 20, 2131, 10.1016/j.cub.2010.10.057 Li, 2008, NOX4 regulates ROS levels under normoxic and hypoxic conditions, triggers proliferation, and inhibits apoptosis in pulmonary artery adventitial fibroblasts, Antioxid. Redox Signal, 10, 1687, 10.1089/ars.2008.2035 Li, 1998, Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production, Biochem. Biophys. Res. Commun, 253, 295, 10.1006/bbrc.1998.9729 Liu, 2005, Redox-dependent transcriptional regulation, Circ. Res, 97, 967, 10.1161/01.RES.0000188210.72062.10 Maltepe, 1998, Oxygen, genes, and development: an analysis of the role of hypoxic gene regulation during murine vascular development, J. Mol. Med, 76, 391, 10.1007/s001090050231 Maltepe, 1997, Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT, Nature, 386, 403, 10.1038/386403a0 Mansfield, 2005, Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation, Cell Metab, 1, 393, 10.1016/j.cmet.2005.05.003 Marshall, 1996, Pulmonary artery NADPH-oxidase is activated in hypoxic pulmonary vasoconstriction, Am. J. Respir. Cell. Mol. Biol, 15, 633, 10.1165/ajrcmb.15.5.8918370 Masson, 2012, The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity, EMBO Rep, 13, 251, 10.1038/embor.2012.9 Maxwell, 1999, The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis, Nature, 399, 271, 10.1038/20459 McCord, 1985, Oxygen-derived free radicals in postischemic tissue injury, N. Engl. J. Med, 3, 159 Mehta, 2009, Proteasomal regulation of the hypoxic response modulates aging in C. elegans, Science, 324, 1196, 10.1126/science.1173507 Michelakis, 1995, Acute hypoxic pulmonary vasoconstriction: a model of oxygen sensing, Physiol. Res, 44, 361 Michelakis, 2002, Diversity in mitochondrial function explains differences in vascular oxygen sensing, Circ. Res, 90, 1307, 10.1161/01.RES.0000024689.07590.C2 Michelakis, 2002, 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, 478, 10.1161/01.RES.0000035057.63303.D1 Mik, 2006, Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX, Nat. Methods, 3, 939, 10.1038/nmeth940 Mills, 1972, Mitochondrial respiratory chain of carotid body and chemoreceptor response to changes in oxygen tension, J. Neurophysiol, 35, 405, 10.1152/jn.1972.35.4.405 Misra, 1972, The univalent reduction of oxygen by reduced flavins and quinones, J. Biol. Chem, 247, 188, 10.1016/S0021-9258(19)45773-6 Mole, 2001, Regulation of HIF by the von Hippel-Lindau tumour suppressor: implications for cellular oxygen sensing, IUBMB Life, 52, 43 Moudgil, 2006, 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, 615, 10.1080/10739680600930222 Mungai, 2011, Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels, Mol. Cell. Biol, 31, 3531, 10.1128/MCB.05124-11 Murphy, 2009, How mitochondria produce reactive oxygen species, Biochem. J., 417, 1, 10.1042/BJ20081386 Murphy, 2011, Unraveling the biological roles of reactive oxygen species, Cell Metab, 13, 361, 10.1016/j.cmet.2011.03.010 Nair, 1986, Two cytochrome oxygen consumption model and mechanism for carotid body chemoreception, Adv. Exp. Med. Biol, 200, 293, 10.1007/978-1-4684-5188-7_36 Orr, 2013, Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening, Free Radic. Biol. Med, 65, 1047, 10.1016/j.freeradbiomed.2013.08.170 Orr, 2015, Suppressors of superoxide production from mitochondrial complex III, Nat. Chem. Biol, 11, 834, 10.1038/nchembio.1910 Ortega-Saenz, 2003, Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells, J. Physiol, 548, 789, 10.1113/jphysiol.2003.039693 Paky, 1993, Endogenous production of superoxide by rabbit lungs: effects of hypoxia or metabolic inhibitors, J. Appl. Physiol, 74, 2868, 10.1152/jappl.1993.74.6.2868 Pearlstein, 2002, Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia, Arterioscler. Thromb. Vasc. Biol, 22, 566, 10.1161/01.ATV.0000012262.76205.6A Quillet-Mary, 1997, Implication of mitochondrial hydrogen peroxide generation in ceramide-induced apoptosis, J. Biol. Chem, 272, 21388, 10.1074/jbc.272.34.21388 Quinlan, 2013, Sites of reactive oxygen species generation by mitochondria oxidizing different substrates, Redox Biol, 1, 304, 10.1016/j.redox.2013.04.005 Rathore, 2006, 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, 784, 10.1016/j.bbrc.2006.10.116 Reeve, 1995, Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue, Exp. Physiol, 80, 825, 10.1113/expphysiol.1995.sp003890 Reeve, 2001, Redox control of oxygen sensing in the rabbit ductus arteriosus, J. Physiol, 533, 253, 10.1111/j.1469-7793.2001.0253b.x Remington, 2006, Fluorescent proteins: maturation, photochemistry and photophysics, Curr. Opin. Struct. Biol, 16, 714, 10.1016/j.sbi.2006.10.001 Rhee, 2012, Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides, J. Biol. Chem, 287, 4403, 10.1074/jbc.R111.283432 Rumsey, 1990, Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat, J. Biol. Chem, 265, 15392, 10.1016/S0021-9258(18)55409-0 Russell, 2005, Mouse models of mitochondrial dysfunction and heart failure, J. Mol. Cell. Cardiol, 38, 81, 10.1016/j.yjmcc.2004.10.010 Sabharwal, 2014, Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel?, Nat. Rev. Cancer, 14, 709, 10.1038/nrc3803 Sabharwal, 2013, Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling, Biochem. J., 456, 337, 10.1042/BJ20130740 Sanjuan-Pla, 2005, A targeted antioxidant reveals the importance of mitochondrial reactive oxygen species in the hypoxic signaling of HIF-1alpha, FEBS Lett, 579, 2669, 10.1016/j.febslet.2005.03.088 Schapira, 1998, Human complex I defects in neurodegenerative diseases, Biochim. Biophys. Acta, 1364, 261, 10.1016/S0005-2728(98)00032-2 Schieber, 2014, TOR signaling couples oxygen sensing to lifespan in C. elegans, Cell Rep, 9, 9, 10.1016/j.celrep.2014.08.075 Schumacker, 2014, Cellular and molecular mechanisms of O2 sensing, 1 Scotti, 2014, Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation, Proc. Natl. Acad. Sci. U.S.A., 111, 13331, 10.1073/pnas.1409916111 Semenza, 2001, HIF-1, O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus, Cell, 107, 1, 10.1016/S0092-8674(01)00518-9 Semenza, 2010, Oxygen homeostasis, Wiley Interdiscip. Rev. Syst. Biol. Med, 2, 336, 10.1002/wsbm.69 Semenza, 2010, Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics, Oncogene, 29, 625, 10.1038/onc.2009.441 Sena, 2012, Physiological roles of mitochondrial reactive oxygen species, Mol. Cell, 48, 158, 10.1016/j.molcel.2012.09.025 Shimada, 1998, Mitochondrial NADH-quinone oxidoreductase of the outer membrane is responsible for paraquat cytotoxicity in rat livers, Arch. Biochem. Biophys, 351, 75, 10.1006/abbi.1997.0557 Shimoda, 2011, HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease, Am. J. Respir. Crit. Care Med, 183, 152, 10.1164/rccm.201009-1393PP Song, 2013, 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, 9662, 10.1074/jbc.M112.440552 Takeda, 2006, 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, 8336, 10.1128/MCB.00425-06 Tarhonskaya, 2015, Kinetic investigations of the role of factor inhibiting hypoxia-inducible factor (FIH) as an oxygen sensor, J. Biol. Chem, 290, 19726, 10.1074/jbc.M115.653014 Thannickal, 2009, Oxygen in the evolution of complex life and the price we pay, Am. J. Respir. Cell Mol. Biol, 40, 507, 10.1165/rcmb.2008-0360PS Tian, 2011, Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitors, J. Biol. Chem, 286, 13041, 10.1074/jbc.M110.211110 Turrens, 1980, Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria, Biochem. J., 191, 421, 10.1042/bj1910421 Turrens, 1985, Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria, Arch. Biochem. Biophys, 237, 408, 10.1016/0003-9861(85)90293-0 Turrens, 1991, Mitochondrial generation of oxygen radicals during reoxygenation of ischemic tissues, Free Radic. Res. Commun, 12–13, 681, 10.3109/10715769109145847 Vanden Hoek, 1997, Significant levels of oxidants are generated by isolated cardiomyocytes during ischemia prior to reperfusion, J. Mol. Cell. Cardiol, 29, 2571, 10.1006/jmcc.1997.0497 Vanden Hoek, 1998, Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes, J. Biol. Chem, 273, 18092, 10.1074/jbc.273.29.18092 Vaux, 2001, Regulation of hypoxia-inducible factor is preserved in the absence of a functioning mitochondrial respiratory chain, Blood, 98, 296, 10.1182/blood.V98.2.296 Votyakova, 2001, DeltaPsi(m)-Dependent and -independent production of reactive oxygen species by rat brain mitochondria, J. Neurochem, 79, 266, 10.1046/j.1471-4159.2001.00548.x Wang, 1995, Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension, Proc. Natl. Acad. Sci. U.S.A., 92, 5510, 10.1073/pnas.92.12.5510 Wang, 2007, Role of mitochondrial reactive oxygen species in hypoxia-dependent increase in intracellular calcium in pulmonary artery myocytes, Free Radic. Biol. Med, 42, 642, 10.1016/j.freeradbiomed.2006.12.008 Wang, 2010, Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells, Respir. Physiol. Neurobiol, 174, 192, 10.1016/j.resp.2010.08.008 Waypa, 2001, Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing, Circ. Res, 88, 1259, 10.1161/hh1201.091960 Waypa, 2002, Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes, Circ. Res, 91, 719, 10.1161/01.RES.0000036751.04896.F1 Waypa, 2006, Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells, Circ. Res, 99, 970, 10.1161/01.RES.0000247068.75808.3f Waypa, 2010, Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells, Circ. Res, 106, 526, 10.1161/CIRCRESAHA.109.206334 Waypa, 2010, Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells, Circ. Res, 106, 526, 10.1161/CIRCRESAHA.109.206334 Waypa, 2013, Superoxide generated at mitochondrial complex III triggers acute responses to hypoxia in the pulmonary circulation, Am. J. Respir. Crit. Care Med, 187, 424, 10.1164/rccm.201207-1294OC Weir, 1995, The mechanism of acute hypoxic pulmonary vasoconstriction: a tale of two channels, FASEB J., 9, 183, 10.1096/fasebj.9.2.7781921 Weir, 2010, The role of redox changes in oxygen sensing, Respir. Physiol. Neurobiol, 174, 182, 10.1016/j.resp.2010.08.015 Weir, 1998, Pulmonary vasoconstriction, oxygen sensing, and the role of ion channels – Thomas A. Neff Lecture, Chest, 114, 17S, 10.1378/chest.114.1_Supplement.17S-a Weir, 2005, Mechanisms of disease – Acute oxygen-sensing mechanisms, N. Engl. J. Med, 353, 2042, 10.1056/NEJMra050002 Welford, 2006, HIF1alpha delays premature senescence through the activation of MIF, Genes Dev, 20, 3366, 10.1101/gad.1471106 Wilson, 1990, Contribution of diffusion to the oxygen dependence of energy metabolism in cells, Experientia, 46, 1160, 10.1007/BF01936927 Wilson, 1988, The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration, J. Biol. Chem, 263, 2712, 10.1016/S0021-9258(18)69126-4 Wilson, 1994, The primary oxygen sensor of the cat carotid body is cytochrome a3 of the mitochondrial respiratory chain, FEBS Lett, 351, 370, 10.1016/0014-5793(94)00887-6 Zhang, 1998, Generation of superoxide anion by succinate-cytochrome c reductase from bovine heart mitochondria, J. Biol. Chem, 273, 33972, 10.1074/jbc.273.51.33972 Zhao, 2007, 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, 319