Semenza, GL. Oxygen homeostasis. WIREs Syst Biol Med 2010, 2:336–361.
Wang, GL, Jiang, BH, Rue, EA, Semenza, GL. Hypoxia‐inducible factor 1 is a basic‐helix‐loop‐helix‐PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 1995, 92:5510–5514.
Prabhakar, NR, Semenza, GL. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia‐inducible factors 1 and 2. Physiol Rev 2012, 92:967–1003.
Duan, C. Hypoxia‐inducible factor 3 biology: complexities and emerging themes. Am J Physiol Cell Physiol 2016, 310:C260–C269.
Berra, E, Roux, D, Richard, DE, Pouysségur, J. Hypoxia‐inducible factor‐1α (HIF‐1α) escapes O2‐driven proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm. EMBO Rep 2001, 2:615–620.
Kaelin, WG Jr, Ratcliffe, PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 2008, 30:393–402.
Maxwell, PH, Wiesener, MS, Chang, GW, Clifford, SC, Vaux, EC, Cockman, ME, Wykoff, CC, Pugh, CW, Maher, ER, Ratcliffe, PJ. The tumor suppressor protein VHL targets hypoxia‐inducible factors for oxygen‐dependent proteolysis. Nature 1999, 399:271–275.
Ivan, M, Haberberger, T, Gervasi, DC, Michelson, KS, Günzler, V, Kondo, K, Yang, H, Sorokina, I, Conaway, RC, Conaway, JW, et al. Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia‐inducible factor. Proc Natl Acad Sci USA 2002, 99:13459–13464.
Waypa, GB, Smith, KA, Schumacker, PT. O2 sensing, mitochondria and ROS signaling: the fog is lifting. Mol Aspects Med 2016, 47–48:76–89.
Lando, D, Peet, DJ, Whelan, DA, Gorman, JJ, Whitelaw, ML. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 2002, 295:858–861.
Mahon, PC, Hirota, K, Semenza, GL. FIH‐1: a novel protein that interacts with HIF‐1α and VHL to mediate repression of HIF‐1 transcriptional activity. Genes Dev 2001, 15:2675–2686.
Lando, D, Peet, DJ, Gorman, JJ, Whelan, DA, Whitelaw, ML, Bruick, RK. FIH‐1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia‐inducible factor. Genes Dev 2002, 16:1466–1471.
Dayan, F, Roux, D, Brahimi‐Horn, MC, Pouyssegur, J, Mazure, NM. The oxygen sensor factor‐inhibiting hypoxia‐inducible factor‐1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia‐inducible factor‐1α. Cancer Res 2006, 66:3688–3698.
Semenza, GL, Wang, GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 1992, 12:5447–5454.
Yoon, D, Pastore, YD, Divoky, V, Liu, E, Mlodnicka, AE, Rainey, K, Ponka, P, Semenza, GL, Schumacher, A, Prchal, JT. Hypoxia‐inducible factor‐1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem 2006, 281:25703–25711.
Shah, YM, Matsubara, T, Ito, S, Yim, SH, Gonzalez, FJ. Intestinal hypoxia‐inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab 2009, 9:152–164.
Mastrogiannaki, M, Matak, P, Keith, B, Simon, MC, Vaulont, S, Peyssonnaux, C. HIF‐2α, but not HIF‐1α, promotes iron absorption in mice. J Clin Invest 2009, 119:1159–1166.
Taylor, M, Qu, A, Anderson, ER, Matsubara, T, Martin, A, Gonzalez, FJ, Shah, YM. Hypoxia‐inducible factor 2α mediates the adaptive increased of intestinal ferroportin during iron deficiency in mice. Gastroenterology 2011, 140:2044–2055.
Rolfs, A, Kvietikova, I, Gassmann, M, Wenger, RH. Oxygen‐regulated transferrin expression is mediated by hypoxia‐inducible factor 1. J Biol Chem 1997, 272:20055–20062.
Lok, CN, Ponka, P. Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem 1999, 274:24147–24152.
Tacchini, L, Bianchi, L, Bernelli‐Zazzera, A, Cairo, G. Transferrin receptor induction by hypoxia. HIF‐1‐mediated transcriptional activation and cell‐specific post‐transcriptional regulation. J Biol Chem 1999, 274:24142–24146.
Liu, YL, Ang, SO, Weigent, DA, Prchal, JT, Bloomer, JR. Regulation of ferrochelatase gene expression by hypoxia. Life Sci 2004, 75:2035–2043.
Ang, SO, Chen, H, Hirota, K, Gordeuk, VR, Jelinek, J, Guan, Y, Liu, E, Sergueeva, AI, Miasnikova, GY, Mole, D, et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet 2002, 32:614–621.
Smith, TG, Brooks, JT, Balanos, GM, Lappin, TR, Layton, DM, Leedham, DL, Liu, C, Maxwell, PH, McMullin, MF, McNamara, CJ, et al. Mutation of von Hippel‐Lindau tumor suppressor and human cardiopulmonary physiology. PLoS Med 2006, 3:e290.
Percy, MJ, Furlow, PW, Beer, PA, Lappin, TR, McMullin, MF, Lee, FS. A novel erythrocytosis‐associated PHD2 mutation suggests the location of a HIF binding groove. Blood 2007, 110:2193–2196.
Percy, MJ, Furlow, PW, Lucas, GS, Li, X, Lappin, TR, McMullin, MF, Lee, FS. A gain‐of‐function mutation in the HIF2A gene in familial erythrocytosis. N Engl J Med 2008, 358:162–168.
Formenti, F, Beer, PA, Croft, QP, Dorrington, KL, Gale, DP, Lappin, TR, Lucas, GS, Maher, ER, Maxwell, PH, McMullin, MF, et al. Cardiopulmonary function in two human disorders of the hypoxia‐inducible factor (HIF) pathway: von Hippel‐Lindau disease and HIF‐2α gain‐of‐function mutation. FASEB J 2011, 25:2001–2011.
Semenza, GL. Hypoxia‐inducible factor 1 and cardiovascular disease. Annu Rev Physiol 2014, 76:39–56.
Rey, S, Semenza, GL. Hypoxia‐inducible factor‐1‐dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res 2010, 86:236–242.
Bosch‐Marce, M, Okuyama, H, Wesley, JB, Sarkar, K, Kimura, H, Liu, YV, Zhang, H, Strazza, M, Rey, S, Savino, L, et al. Effects of aging and hypoxia‐inducible factor‐1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia. Circ Res 2007, 101:1310–1318.
Sarkar, K, Fox‐Talbot, K, Steenbergen, C, Bosch‐Marcé, M, Semenza, GL. Adenoviral transfer of HIF‐1α enhances vascular responses to critical limb ischemia in diabetic mice. Proc Natl Acad Sci USA 2009, 106:18769–18774.
Rey, S, Lee, K, Wang, CJ, Gupta, K, Chen, S, McMillan, A, Bhise, N, Levchenko, A, Semenza, GL. Synergistic effect of HIF‐1α gene therapy and HIF‐1‐activated bone marrow‐derived angiogenic cells in a mouse model of limb ischemia. Proc Natl Acad Sci USA 2009, 106:20399–20404.
Rey, S, Luo, W, Shimoda, LA, Semenza, GL. Metabolic reprogramming by HIF‐1 promotes the survival of bone marrow‐derived angiogenic cells in ischemic tissue. Blood 2011, 117:4988–4998.
Resar, JR, Roguin, A, Voner, J, Nasir, K, Hennebry, TA, Miller, JM, Ingersoll, R, Kasch, LM, Semenza, GL. Hypoxia‐inducible factor 1α polymorphism and coronary collaterals in patients with ischemic heart disease. Chest 2005, 128:787–791.
Hlatky, MA, Quertermous, T, Boothroyd, DB, Priest, JR, Glassford, AJ, Myers, RM, Fortmann, SP, Iribarren, C, Tabor, HK, Assimes, TL, et al. Polymorphisms in hypoxia‐inducible factor 1 and the initial clinical presentation of coronary disease. Am Heart J 2007, 154:1035–1042.
Campochiaro, PA. Ocular neovascularization. J Mol Med 2013, 91:311–321.
Aiello, LP, Avery, RL, Arrigg, PG, Keyt, BA, Jampel, HD, Shah, ST, Pasquale, LR, Thieme, H, Iwamoto, MA, Park, JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994, 331:1480–1487.
Ozaki, H, Yu, AY, Della, N, Ozaki, K, Luna, JD, Yamada, H, Hackett, SF, Okamoto, N, Zack, DJ, Semenza, GL, et al. Hypoxia inducible factor‐1α is increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest Ophthalmol Vis Sci 1999, 40:182–189.
Ip, MS, Domalpally, A, Hopkins, JJ, Wong, P, Ehrlich, JS. Long‐term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol 2012, 130:1145–1152.
Yoshida, T, Zhang, H, Iwase, T, Shen, J, Semenza, GL, Campochiaro, PA. Digoxin inhibits retinal ischemia‐induced HIF‐1α expression and ocular neovascularization. FASEB J 2010, 24:1759–1767.
Babapoor‐Farrokhran, S, Jee, K, Puchner, B, Hassan, SJ, Xin, X, Rodrigues, M, Kashiwabuchi, F, Ma, T, Hu, K, Deshpande, M, et al. Angiopoietin‐like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy. Proc Natl Acad Sci USA 2015, 112:E3030–E3039.
Xin, X, Rodrigues, M, Umapathi, M, Kashiwabuchi, F, Ma, T, Babapoor‐Farrokhran, S, Wang, S, Hu, J, Bhutto, I, Welsbie, DS, et al. Hypoxic retinal Muller cells promote vascular permeability by HIF‐1‐dependent up‐regulation of angiopoietin‐like 4. Proc Natl Acad Sci USA 2013, 110:E3425–E3434.
Zhang, H, Qian, DZ, Tan, YS, Lee, K, Gao, P, Ren, YR, Rey, S, Hammers, H, Chang, D, Pili, R, et al. Digoxin and other cardiac glycosides inhibit HIF‐1α synthesis and block tumor growth. Proc Natl Acad Sci USA 2008, 105:19579–19586.
Lee, K, Qian, DZ, Rey, S, Wei, H, Liu, JO, Semenza, GL. Anthracycline chemotherapy inhibits HIF‐1 transcriptional activity and tumor‐induced mobilization of circulating angiogenic cells. Proc Natl Acad Sci USA 2009, 106:2353–2358.
Lee, K, Zhang, H, Qian, DZ, Rey, S, Liu, JO, Semenza, GL. Acriflavine inhibits HIF‐1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA 2009, 106:17910–17915.
Iwase, T, Fu, J, Yoshida, T, Muramatsu, D, Miki, A, Hashida, N, Lu, L, Oveson, B, Lima e Silva, R, Seidel, C, et al. Sustained delivery of a HIF‐1 antagonist for ocular neovascularization. J Control Release 2013, 172:625–633.
Vaupel, P, Hockel, M, Mayer, A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal 2007, 9:1221–1235.
Carracedo, A, Cantley, LC, Pandolfi, PP. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer 2013, 13:227–232.
Semenza, GL. HIF‐1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 2013, 123:3664–3671.
Kim, JW, Tchernyshyov, I, Semenza, GL, Dang, CV. HIF‐1‐mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006, 3:177–185.
Papandreou, I, Cairns, RA, Fontana, L, Denko, NC. HIF‐1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006, 3:187–197.
Lu, CW, Lin, SC, Chen, KF, Lai, YY, Tsai, SJ. Induction of pyruvate dehydrogenase kinase‐3 by hypoxia‐inducible factor 1 promotes metabolic switch and drug resistance. J Biol Chem 2008, 283:28106–28114.
Le, A, Cooper, CR, Gouw, AM, Dinavahi, R, Maitra, A, Deck, LM, Royer, RE, Vander Jagt, DL, Semenza, GL, Dang, CV. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA 2010, 107:2037–2042.
Zhang, H, Bosch‐Marce, M, Shimoda, LA, Tan, YS, Baek, JH, Wesley, JB, Gonzalez, FJ, Semenza, GL. Mitochondrial autophagy is an HIF‐1‐dependent adaptive metabolic response to hypoxia. J Biol Chem 2008, 283:10892–10903.
Bellot, G, Garcia‐Medina, R, Gounon, P, Chiche, J, Roux, D, Pouysségur, J, Mazure, NM. Hypoxia‐induced autophagy is mediated through hypoxia‐inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 2009, 29:2570–2581.
Huang, D, Li, T, Li, X, Zhang, L, Sun, L, He, X, Zhong, X, Jia, D, Song, L, Semenza, GL, et al. HIF‐1‐mediated suppression of acyl‐CoA dehydrogenases and fatty acid oxidation is critical for cancer progression. Cell Rep 2014, 25:1930–1942.
Currie, E, Schulze, A, Zechner, R, Walther, TC, Farese, RV Jr. Cellular fatty acid metabolism and cancer. Cell Metab 2013, 18:153–161.
Samudio, I, Harmancey, R, Fiegl, M, Kantarjian, H, Konopleva, M, Korchin, B, Kaluarachchi, K, Bornmann, W, Duvvuri, S, Taegtmeyer, H, et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 2010, 120:142–156.
Camarda, R, Zhou, AY, Kohnz, RA, Balakrishnan, S, Mahieu, C, Anderton, B, Eyob, H, Kajimura, S, Krings, G, Nomura, DK, et al. Inhibition of fatty acid oxidation as a therapy for MYC‐overexpressing triple‐negative breast cancer. Nat Med 2016, 22:427–432.
Fan, J, Ye, J, Kamphorst, JJ, Shlomi, T, Thompson, CB, Rabinowitz, JD. Quantitative flux analysis reveals folate‐dependent NADPH production. Nature 2014, 510:298–302.
Samanta, D, Park, Y, Andrabi, SA, Shelton, LM, Gilkes, DM, Semenza, GL. PHGDH expression is required for mitochondrial redox homeostasis, breast cancer stem cell maintenance, and lung metastasis. Cancer Res 2016, 76:4430–4442.
Ye, J, Fan, J, Venneti, S, Wan, YW, Pawel, BR, Zhang, J, Finley, LW, Lu, C, Lindsten, T, Cross, JR, et al. Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov 2014, 4:1406–1417.
Kim, D, Fiske, BP, Birsoy, K, Freinkman, E, Kami, K, Possemato, RL, Chudnovsky, Y, Pacold, ME, Chen, WW, Cantor, JR, et al. SHMT2 drives glioma cell survival in ischemia but imposes a dependence on glycine clearance. Nature 2015, 520:363–367.
Lu, H, Samanta, D, Xiang, L, Zhang, H, Hu, H, Chen, I, Bullen, JW, Semenza, GL. Chemotherapy triggers HIF‐1‐dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. Proc Natl Acad Sci USA 2015, 112:E4600–E4609.
Pflüger, E. Ueber die ursache der athembewegungen, sowie der dyspnoë und apnoë. Pflügers Arch Gesamte Physiol Meschen Tiere 1868, 1:61–106.
De Castro, F. Sur la structure et l`innervation de la glande intercarotidienne (glomus caroticum) de l`homme et des mammiferes et sur un nouveau systeme de l`innervation autonome du nerf glossopharyngien. Trav Lab Rech Biol 1926, 24:365–432.
Heymans, J, Heymans, C. Sur les modifications directes et sur la regulation reflexe de l`activitie du centre respiratory de la tete isolee du chien. Arch Int Pharmacodyn Ther 1927, 33:273–372.
Prabhakar, NR, Semenza, GL. Gaseous messengers in oxygen sensing. J Mol Med 2012, 90:265–272.
Prabhakar, NR, Semenza, GL. Oxygen sensing and homeostasis. Physiology 2015, 30:340–348.
Yuan, G, Vasavda, C, Peng, YJ, Makarenko, VV, Raghuraman, G, Nanduri, J, Gadalla, MM, Semenza, GL, Kumar, GK, Snyder, SH, et al. Protein kinase G‐regulated production of H2S governs oxygen sensing. Sci Signal 2015, 8:ra37.
Peng, YJ, Nanduri, J, Raghuraman, G, Souvannakitti, D, Gadalla, MM, Kumar, GK, Snyder, SH, Prabhakar, NR. H2S mediates O2 sensing in the carotid body. Proc Natl Acad Sci USA 2010, 107:10719–10724.
Kline, DD, Peng, YJ, Manalo, DJ, Semenza, GL, Prabhakar, NR. Defective carotid body function and impaired ventilator responses to chronic hypoxia in mice partially deficient for hypoxia‐inducible factor 1α. Proc Natl Acad Sci USA 2002, 99:821–826.
Nieto, FJ, Young, TB, Lind, BK, Shahar, E, Samet, JM, Redline, S, D`Agostino, RB, Newman, AB, Lebowitz, MD, Pickering, TG. Association of sleep‐disordered breathing, sleep apnea, and hypertension in a large community‐based study. Sleep Heart Health Study. JAMA 2000, 283:1829–1836.
Fletcher, EC, Lesske, J, Behm, R, Miller, CC 3rd, Stauss, H, Unger, T. Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea. J Appl Physiol 1992, 72:1978–1984.
Peng, YJ, Yuan, G, Ramakrishnan, D, Sharma, SD, Bosch‐Marce, M, Kumar, GK, Semenza, GL, Prabhakar, NR. Heterozygous HIF‐1α deficiency impairs carotid body‐mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia. J Physiol 2006, 577:705–716.
Yuan, G, Khan, SA, Luo, W, Nanduri, J, Semenza, GL, Prabhakar, NR. Hypoxia‐inducible factor 1 mediates increased expression of NADPH oxidase‐2 in response to intermittent hypoxia. J Cell Physiol 2011, 226:2925–2933.
Yuan, G, Nanduri, J, Khan, S, Semenza, GL, Prabhakar, NR. Induction of HIF‐1α expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol 2008, 217:674–685.
Nanduri, J, Wang, N, Yuan, G, Khan, SA, Souvannakitti, D, Peng, YJ, Kumar, GK, Garcia, JA, Prabhakar, NR. Intermittent hypoxia degrades HIF‐2α via calpains resulting in oxidative stress: implications for recurrent apnea‐induced morbidities. Proc Natl Acad Sci USA 2009, 106:1199–1204.
Peng, YJ, Nanduri, J, Khan, SA, Yuan, G, Wang, N, Kinsman, B, Vaddi, DR, Kumar, GK, Garcia, JA, Semenza, GL, et al. Hypoxia‐inducible factor 2α (HIF‐2α) heterozygous‐ mice exhibit exaggerated carotid body sensitivity to hypoxia, breathing instability, and hypertension. Proc Natl Acad Sci USA 2011, 108:3065–3070.
Yuan, G, Peng, YJ, Reddy, VD, Makarenko, VV, Nanduri, J, Khan, SA, Garcia, JA, Kumar, GK, Semenza, GL, Prabhakar, NR. Mutual antagonism between hypoxia‐inducible factors 1α and 2α regulates oxygen sensing and cardio‐respiratory homeostasis. Proc Natl Acad Sci USA 2013, 110:E1788–E1796.
Yuan, G, Peng, YJ, Khan, SA, Nanduri, J, Singh, A, Vasavda, C, Semenza, GL, Kumar, GK, Snyder, SH, Prabhakar, NR. H2S production by reactive oxygen species in the carotid body triggers hypertension in a rodent model of sleep apnea. Sci Signal 2016, 9:ra80.
Iyer, NV, Kotch, LE, Agani, F, Leung, SW, Laughner, E, Wenger, RH, Gassmann, M, Gearhart, JD, Lawler, AM, Yu, AY, et al. Cellular and developmental control of O2 homeostasis by hypoxia‐inducible factor 1α. Genes Dev 1998, 12:149–162.
Maxwell, PH, Eckardt, KU. HIF prolyl hydroxylase inhibitors for the treatment of renal anemia and beyond. Nat Rev Nephrol 2016, 12:157–168.
Semenza, GL. The hypoxic tumor microenvironment: a driving force for breast cancer progression. Biochim Biophys Acta 2016, 1863:382–391.