Cited by 332Cancer, Hypoxia, and MetabolismMetal-Catalyzed Oxygenation MechanismsErythropoietin and Anemia Treatment

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

Multiple Factors Affecting Cellular Redox Status and Energy Metabolism Modulate Hypoxia-Inducible Factor Prolyl Hydroxylase Activity In Vivo and In Vitro

Open access

Pan, Yi, Mansfield, Kyle D., Bertozzi, Cara C., Rudenko, Viktoriya, Chan, Denise A., Giaccia, Amato J., Simon, M. Celeste·2007·Molecular and Cellular Biology

DOI 10.1128/mcb.01223-06PMC PMC1800695

Open this paper in CoChat — free account

Abstract

Prolyl hydroxylation of hypoxible-inducible factor alpha (HIF-alpha) proteins is essential for their recognition by pVHL containing ubiquitin ligase complexes and subsequent degradation in oxygen (O(2))-replete cells. Therefore, HIF prolyl hydroxylase (PHD) enzymatic activity is critical for the regulation of cellular responses to O(2) deprivation (hypoxia). Using a fusion protein containing the human HIF-1alpha O(2)-dependent degradation domain (ODD), we monitored PHD activity both in vivo and in cell-free systems. This novel assay allows the simultaneous detection of both hydroxylated and nonhydroxylated PHD substrates in cells and during in vitro reactions. Importantly, the ODD fusion protein is regulated with kinetics identical to endogenous HIF-1alpha during cellular hypoxia and reoxygenation. Using in vitro assays, we demonstrated that the levels of iron (Fe), ascorbate, and various tricarboxylic acid (TCA) cycle intermediates affect PHD activity. The intracellular levels of these factors also modulate PHD function and HIF-1alpha accumulation in vivo. Furthermore, cells treated with mitochondrial inhibitors, such as rotenone and myxothiazol, provided direct evidence that PHDs remain active in hypoxic cells lacking functional mitochondria. Our results suggest that multiple mitochondrial products, including TCA cycle intermediates and reactive oxygen species, can coordinate PHD activity, HIF stabilization, and cellular responses to O(2) depletion.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1128/mcb.01223-06

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 7×
“HIF- protein turnover is ensured by hydroxylation of critical proline residues within the oxygendependent degradation domains (ODDs) (23), allowing their association with von Hippel-Lindau protein (pVHL)-containing E3 ubiquitin ligase complexes (7, 16, 21, 27 , 28, 44, 58).”
BackgroundMethodInfluential
HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia
Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108 · cited 4×
“Not surprisingly, succinate functions as a competitive inhibitor which is reversible by -ketoglutarate (35, 54 ).”
BackgroundInfluentialSelf-citation

Show all 59 references

Research works printed but not linked: 2

Bardos J. I., 2005, Biochim. Biophys. Acta, 1755, 107
Knowles H. J., 2003, Cancer Res., 63, 1764

Sorted by citations

Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601
Retracted
Hypoxic control of metastasis
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340
Self-citation
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272
Self-citation
Hydrogen peroxide sensing, signaling and regulation of transcription factors
Marinho, H. S., Real, C., Cyrne, L., Soares, H., & Antunes, F. (2014) · Redox Biology · doi:10.1016/j.redox.2014.02.006 · Cited by 872
Hypoxia and mitochondrial oxidative metabolism
Solaini, G., Baracca, A., Lenaz, G., & Sgarbi, G. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.011 · Cited by 628
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588
The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production
Bell, E. L., Klimova, T. A., Eisenbart, J., Moraes, C. T., Murphy, M. P., Budinger, G. R. S., & Chandel, N. S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200609074 · Cited by 568
The updated biology of hypoxia-inducible factor
Greer, S. N., Metcalf, J. L., Wang, Y., & Ohh, M. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.125 · Cited by 545
ROS in Cancer: The Burning Question
Chio, I. I. C., & Tuveson, D. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.004 · Cited by 532
Oxygen availability and metabolic adaptations
Nakazawa, M. S., Keith, B., & Simon, M. C. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.84 · Cited by 446
Self-citation
Mitochondrial complex III regulates hypoxic activation of HIF
Klimova, T., & Chandel, N. S. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402307 · Cited by 433
Role and regulation of prolyl hydroxylase domain proteins
Fong, G.-H., & Takeda, K. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.10 · Cited by 437
Hypoxia-induced reactive oxygen species formation in skeletal muscle
Clanton, T. L. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01298.2006 · Cited by 401
Pyruvate Dehydrogenase Complex Activity Controls Metabolic and Malignant Phenotype in Cancer Cells
McFate, T., Mohyeldin, A., Lu, H., Thakar, J. H., Henriques, J., Halim, N. D., Wu, H., Schell, M. J., Tsang, T. M., Teahan, O., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801765200 · Cited by 395
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer
Bae, T., Hallis, S. P., & Kwak, M. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01180-8 · Cited by 410
Role of reactive oxygen and nitrogen species in the vascular responses to inflammation
Kvietys, P. R., & Granger, D. N. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.11.002 · Cited by 319
Oxygen sensing and hypoxia signalling pathways in animals: The implications of physiology for cancer
Ratcliffe, P. J. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.251470 · Cited by 294
The Redox Basis of Epigenetic Modifications: From Mechanisms to Functional Consequences
Cyr, A. R., & Domann, F. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3492 · Cited by 301
Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis
Sato, S., Basse, A. L., Schönke, M., Chen, S., Samad, M., Altıntaş, A., Laker, R. C., Dalbram, E., Barrès, R., Baldi, P., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.013 · Cited by 298
NRF2 Blockade Suppresses Colon Tumor Angiogenesis by Inhibiting Hypoxia-Induced Activation of HIF-1α
Kim, T., Hur, E.-G., Kang, S., Kim, J., Thapa, D., Lee, Y. M., Ku, S., Jung, Y., & Kwak, M. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3007 · Cited by 292
Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis
Takeda, Y., Costa, S., Delamarre, E., Roncal, C., de Oliveira, R. L., Squadrito, M. L., Finisguerra, V., Deschoemaeker, S., Bruyére, F., Wenes, M., et al. (2011) · Nature · doi:10.1038/nature10507 · Cited by 290
Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney
Legrand, M. M., Mik, E. G., Johannes, T., Payen, D. M., & İnce, C. (2008) · Molecular Medicine · doi:10.2119/2008-00006.legrand · Cited by 290
Contribution of metabolic reprogramming to macrophage plasticity and function
Kasmi, K. C. E., & Stenmark, K. R. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.09.001 · Cited by 281
Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets
Myllyharju, J. (2008) · Annals of Medicine · doi:10.1080/07853890801986594 · Cited by 269
Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets
Zhao, Y., Xiong, W., Li, C., Zhao, R., Lu, H., Song, S., Zhou, Y., Hu, Y., Shi, B., & Ge, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01652-9 · Cited by 275
Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells
Jung, S., Yang, W. K., Kim, J., Kim, H. S., Kim, E. J., Yun, H., Park, H., Kim, S. S., Choe, W., Kang, I., et al. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn032 · Cited by 257
Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review
Riegger, J., Schoppa, A., Ruths, L., Haffner‐Luntzer, M., & Ignatius, A. A. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00489-y · Cited by 272
Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function
McNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234
Non-Canonical Mechanisms Regulating Hypoxia-Inducible Factor 1 Alpha in Cancer
Iommarini, L., Porcelli, A. M., Gasparre, G., & Kurelac, I. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00286 · Cited by 231
Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies
Ebbesen, P., Pettersen, E. O., Gorr, T. A., Jobst, G., Williams, K. J., Kieninger, J., Wenger, R. H., Pastoreková, S., Dubois, L. J., Lambin, P., et al. (2009) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756360902784425 · Cited by 221
Hypoxia/pseudohypoxia‐mediated activation of hypoxia‐inducible factor‐1α in cancer
Hayashi, Y., Yokota, A., Harada, H., & Huang, G. (2019) · Cancer Science · doi:10.1111/cas.13990 · Cited by 229
Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria
Thomas, L. W., & Ashcroft, M. A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03039-y · Cited by 219
Stable isotope-resolved metabolomics and applications for drug development
Fan, T. W. ‐., Lorkiewicz, P., Sellers, K., Moseley, H., Higashi, R. M., & Lane, A. N. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.12.007 · Cited by 215
LncRNAs regulate metabolism in cancer
Lin, W., Zhou, Q., Wang, C., Zhu, L., Bi, C., Zhang, S., Wang, X., & Jin, H. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.40769 · Cited by 208
Mechanisms of adaptive angiogenesis to tissue hypoxia
Fong, G. (2008) · Angiogenesis · doi:10.1007/s10456-008-9107-3 · Cited by 212
Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia
Sulkshane, P., Ram, J., Thakur, A., Reis, N., Kleifeld, O., & Glickman, M. H. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102047 · Cited by 201
Reactive Oxygen Species Regulate Hypoxia-Inducible Factor 1α Differentially in Cancer and Ischemia
Qutub, A. A., & Popel, A. S. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00060-08 · Cited by 196
Whole-Exome Sequencing Identifies MDH2 as a New Familial Paraganglioma Gene
Cascón, A., Comino‐Méndez, I., Currás-Freixes, M., de Cubas, A. A., Contreras, L., Richter, S., Peitzsch, M., Mančíková, V., Inglada‐Pérez, L., Pérez‐Barrios, A., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv053 · Cited by 204
Stabilization of Hypoxia-inducible Factor-1α Protein in Hypoxia Occurs Independently of Mitochondrial Reactive Oxygen Species Production
Chua, Y. L., Dufour, E., Dassa, E. P., Rustin, P., Jacobs, H. T., Taylor, C. T., & Hagen, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.158485 · Cited by 189
Reactive oxygen species and cellular oxygen sensing
Cash, T. P., Pan, Y., & Simon, M. C. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.07.001 · Cited by 195
Self-citation
Hypoxia-inducible hydrogels
Park, K. M., & Gerecht, S. (2014) · Nature Communications · doi:10.1038/ncomms5075 · Cited by 193
Hypoxia-inducible Factor-1α Stabilization in Nonhypoxic Conditions: Role of Oxidation and Intracellular Ascorbate Depletion
Pagé, E. L., Chan, D. A., Giaccia, A. J., Levine, M., & Richard, D. E. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-06-0612 · Cited by 181
Self-citation
Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair
Mikhed, Y., Görlach, A., Knaus, U. G., & Daiber, A. (2015) · Redox Biology · doi:10.1016/j.redox.2015.05.008 · Cited by 189
Hypoxia and HIF Signaling: One Axis with Divergent Effects
Corrado, C., & Fontana, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165611 · Cited by 184
Molecular Mechanisms of High-Altitude Acclimatization
Mallet, R. T., Burtscher, J., Pialoux, V., Pasha, Q., Ahmad, Y., Millet, G. P., & Burtscher, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021698 · Cited by 200
Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1α-induced metabolic reprograming
Zhao, F., Mancuso, A., Bui, T. V., Tong, X., Gruber, J. J., Swider, C. R., Sanchez, P. V., Lum, J. J., Sayed, N., Melo, J. V., et al. (2010) · Oncogene · doi:10.1038/onc.2010.67 · Cited by 179
NQO1 inhibits proteasome-mediated degradation of HIF-1α
Oh, E., Kim, J., Kim, J. M., Kim, S., Lee, J., Hong, S., Goodwin, J., Ruthenborg, R. J., Jung, M. G., Lee, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms13593 · Cited by 183
Hypoxia‐mediated biological control
Cassavaugh, J. M., & Lounsbury, K. M. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22956 · Cited by 177
Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver
Doğuer, Ç., Ha, J., & Collins, J. F. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170045 · Cited by 225
Ascorbate as a co-factor for Fe- and 2-oxoglutarate dependent dioxygenases: Physiological activity in tumor growth and progression
Kuiper, C., & Vissers, M. C. M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00359 · Cited by 163
Carbon Monoxide Promotes VEGF Expression by Increasing HIF-1α Protein Level via Two Distinct Mechanisms, Translational Activation and Stabilization of HIF-1α Protein
Choi, Y. K., Kim, C. K., Lee, H., Jeoung, D., Ha, K., Kwon, Y.-G., Kim, K. W., & Kim, Y. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.131284 · Cited by 166
Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1α Activation
Lee, G., Won, H., Lee, Y.-M., Choi, J.-W., Oh, T.-I., Jang, J.-H., Choi, D., Lim, B. O., Kim, Y. J., Park, J., et al. (2016) · Scientific Reports · doi:10.1038/srep18928 · Cited by 166
Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics
Lehtonen, H. J. (2011) · Familial Cancer · doi:10.1007/s10689-011-9428-z · Cited by 156
Multiscale models of angiogenesis
Qutub, A. A., Gabhann, F. M., Karagiannis, E. D., Vempati, P., & Popel, A. S. (2009) · IEEE Engineering in Medicine and Biology Magazine · doi:10.1109/memb.2009.931791 · Cited by 153
Cellular and molecular mechanisms in the hypoxic tissue: role of HIF‐1 and ROS
Zepeda, A. B., Pessoa, A., Castillo, R. L., Figueroa, C. A., Pulgar, V. M., & Farías, J. G. (2013) · Cell Biochemistry and Function · doi:10.1002/cbf.2985 · Cited by 151
Adaptive Responses to Hypoxia and/or Hyperoxia in Humans
Burtscher, J., Mallet, R. T., Pialoux, V., Millet, G. P., & Burtscher, M. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0280 · Cited by 182
The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity
Masson, N., Singleton, R. S., Sekirnik, R., Trudgian, D. C., Ambrose, L. J. A., Miranda, M. X., Tian, Y., Kessler, B. M., Schofield, C. J., & Ratcliffe, P. J. (2012) · EMBO Reports · doi:10.1038/embor.2012.9 · Cited by 148
Regulation of angiogenesis by oxygen sensing mechanisms
Fong, G. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0458-z · Cited by 143
HIF-independent role of prolyl hydroxylases in the cellular response to amino acids
Durán, R. V., MacKenzie, E. D., Boulahbel, H., Frezza, C., Heiserich, L., Tardito, S., Bussolati, O., Rocha, S., Hall, M. N., & Gottlieb, E. (2013) · Oncogene · doi:10.1038/onc.2012.465 · Cited by 139
Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment
Justus, C., Sanderlin, E. J., & Yang, L. V. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160511055 · Cited by 139
Redox Regulation via Glutaredoxin-1 and Protein S -Glutathionylation
Matsui, R., Ferrán, B., Oh, A., Croteau, D., Shao, D., Han, J., Pimentel, D. R., & Bachschmid, M. M. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7963 · Cited by 142
Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells
Azimi, I., Petersen, R. M., Thompson, E. W., Roberts‐Thomson, S. J., & Monteith, G. R. (2017) · Scientific Reports · doi:10.1038/s41598-017-15474-7 · Cited by 141
Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo
Milovanova, T. N., Bhopale, V. M., Sorokina, E. M., Moore, J. S., Hunt, T. K., Hauer‐Jensen, M., Velazquez, O. C., & Thom, S. R. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91054.2008 · Cited by 139
The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity
Vatrinet, R., Leone, G., Luise, M. D., Girolimetti, G., Vidone, M., Gasparre, G., & Porcelli, A. M. (2017) · Cancer & Metabolism · doi:10.1186/s40170-017-0165-0 · Cited by 133
Strange Bedfellows: Nuclear Factor, Erythroid 2-Like 2 (Nrf2) and Hypoxia-Inducible Factor 1 (HIF-1) in Tumor Hypoxia
Toth, R. K., & Warfel, N. A. (2017) · Antioxidants · doi:10.3390/antiox6020027 · Cited by 136
LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect
Xiang, S., Gu, H., Jin, L., Thorne, R. F., Zhang, X. D., & Wu, M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711257115 · Cited by 129
Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets
Miyata, T., Takizawa, S., & de Strihou, C. V. Y. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00430.2010 · Cited by 131
Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis
Chacko, B. K., Srivastava, A., Johnson, M. S., Benavides, G. A., Chang, M. J., Ye, Y., Jhala, N., Murphy, M. P., Kalyanaraman, B., & Darley-Usmar, V. M. (2011) · Hepatology · doi:10.1002/hep.24377 · Cited by 122
Molecular Mediators Governing Iron-Copper Interactions
Güleç, Ş., & Collins, J. F. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161215 · Cited by 122
The mTOR and PP2A pathways regulate PHD2 phosphorylation to fine-tune HIF1α levels and colorectal cancer cell survival under hypoxia
Di Conza, G., Trusso Cafarello, S., Loroch, S., Mennerich, D., Deschoemaeker, S., Di Matteo, M., Ehling, M., Gevaert, K., Prenen, H., Zahedi, R. P., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.051 · Cited by 119
Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree?
Bayley, J., & Devilee, P. (2010) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.02.008 · Cited by 119
Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo
Harris, J. M., Esain, V., Frechette, G. M., Harris, L. J., Cox, A. G., Cortes, M., Garnaas, M., Carroll, K. J., Cutting, C. C., Khan, T. M., et al. (2013) · Blood · doi:10.1182/blood-2012-12-471201 · Cited by 116
Hypoxia-inducible factor 1–mediated characteristic features of cancer cells for tumor radioresistance
Harada, H. (2016) · Journal of Radiation Research · doi:10.1093/jrr/rrw012 · Cited by 116
Knockdown of Nrf2 suppresses glioblastoma angiogenesis by inhibiting hypoxia-induced activation of HIF-1α
Ji, X., Wang, H., Zhu, J., Zhu, L., Pan, H., Li, W., Zhou, Y., Cong, Z., Yan, F., & Chen, S. (2013) · International Journal of Cancer · doi:10.1002/ijc.28699 · Cited by 111
Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
Miller, D. J., Cascio, M. A., & Rosca, M. G. (2020) · Antioxidants · doi:10.3390/antiox9100905 · Cited by 116
Placental metabolic reprogramming: do changes in the mix of energy-generating substrates modulate fetal growth?
Illsley, N. P., Caniggia, I., & Zamudio, S. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082798ni · Cited by 107
The interplay of hypoxic and mental stress: Implications for anxiety and depressive disorders
Burtscher, J., Niedermeier, M., Hüfner, K., van den Burg, E. H., Kopp, M., Stoop, R., Burtscher, M., Gatterer, H., & Millet, G. P. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104718 · Cited by 110
Clinical iron deficiency disturbs normal human responses to hypoxia
Frise, M. C., Cheng, H., Nickol, A. H., Curtis, M. K., Pollard, K. A., Roberts, D. J., Ratcliffe, P. J., Dorrington, K. L., & Robbins, P. A. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85715 · Cited by 106
Mutual Antagonism of Hypoxia-Inducible Factor Isoforms in Cardiac, Vascular, and Renal Disorders
Packer, M. (2020) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2020.05.006 · Cited by 103
ASB4 Is a Hydroxylation Substrate of FIH and Promotes Vascular Differentiation via an Oxygen-Dependent Mechanism
Ferguson, J. E., Wu, Y., Smith, K. R., Charles, P. C., Powers, K. T., Wang, H., & Patterson, C. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00511-07 · Cited by 103
Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation
Zhang, H., Zhang, G., Gonzalez, F. J., Park, S.-M., & Cai, D. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001112 · Cited by 105
Oxygen versus Reactive Oxygen in the Regulation of HIF-1α: The Balance Tips
Hagen, T. (2012) · Biochemistry Research International · doi:10.1155/2012/436981 · Cited by 100
Mitochondria control acute and chronic responses to hypoxia
McElroy, G. S., & Chandel, N. S. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.03.034 · Cited by 100
Atypical CRM1-dependent Nuclear Export Signal Mediates Regulation of Hypoxia-inducible Factor-1α by MAPK
Mylonis, I., Chachami, G., Paraskeva, E., & Simos, G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803081200 · Cited by 96
Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression
Yang, J., Staples, O. D., Thomas, L. W., Briston, T., Robson, M. P., Poon, E., Simões, M. L., El‐Emir, E., Buffa, F. M., Ahmed, A., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58780 · Cited by 93
Redox regulation of macrophages
Tran, N., & Mills, E. L. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103123 · Cited by 101
A Central Role for Hypoxic Signaling in Cartilage, Bone, and Hematopoiesis
Rankin, E. B., Giaccia, A. J., & Schipani, E. (2011) · Current Osteoporosis Reports · doi:10.1007/s11914-011-0047-2 · Cited by 93
Self-citation
The Hypoxia-Inducible Factor-2α Is Stabilized by Oxidative Stress Involving NOX4
Diebold, I., Flügel, D., Becht, S., BelAiba, R. S., Bonello, S., Hess, J., Kietzmann, T., & Görlach, A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.3014 · Cited by 92
Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response
Lall, R., Ganapathy, S., Yang, M., Xiao, S., Teng, X., Su, H., Shadfan, M., Asara, J. M., Ha, C. S., Ben‐Sahra, I., et al. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.24 · Cited by 96
HIF-mediated innate immune responses: cell signaling and therapeutic implications
Walmsley, S. R., Harris, A. J., Thompson, A. A. R., & Whyte, M. K. B. (2014) · Hypoxia · doi:10.2147/hp.s50269 · Cited by 93
Mitochondrial oxygen sensing: regulation of hypoxia-inducible factor by mitochondrial generated reactive oxygen species
Bell, E. L., & Chandel, N. S. (2007) · Essays in Biochemistry · doi:10.1042/bse0430017 · Cited by 90
HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression
Tennant, D. A., & Gottlieb, E. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0627-0 · Cited by 83
Oxidative Stress and Hypoxia Contribute to Alzheimer's Disease Pathogenesis: Two Sides of the Same Coin
Guglielmotto, M., Tamagno, E., & Danni, O. (2009) · The Scientific World JOURNAL · doi:10.1100/tsw.2009.93 · Cited by 82
Nicotinamide nucleotide transhydrogenase (NNT) deficiency dysregulates mitochondrial retrograde signaling and impedes proliferation
Ho, H., Lin, Y.-T., Lin, G., Wu, P., & Cheng, M. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.035 · Cited by 81
The twisted survivin connection to angiogenesis
Sanhueza, C. T., Wehinger, S., Bennett, J., Valenzuela, M., Owen, G. I., & Quest, A. F. G. (2015) · Molecular Cancer · doi:10.1186/s12943-015-0467-1 · Cited by 88
Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of Hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition
Chintala, S., Najrana, T., Tóth, K., Cao, S., Durrani, F. A., Пили, Р., & Rustum, Y. M. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-293 · Cited by 81
Inducible glomerular erythropoietin production in the adult kidney
Broeker, K. A. E., Miquerol, L., Todorov, V., Hugo, C., Adams, R. H., Kurtz, A., & Kurt, B. (2015) · Kidney International · doi:10.1038/ki.2015.274 · Cited by 77
Oxygen-sensing under the influence of nitric oxide
Berchner‐Pfannschmidt, U., Tug, S., Kirsch, M., & Fandrey, J. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.10.004 · Cited by 78
Journal of Parkinson’s disease & Alzheimer’s disease
Gottschalk, W. K., Lutz, M. W., He, Y. T., Saunders, A. M., Burns, D. K., Roses, A. D., & Chiba‐Falek, O. (2014) · Journal of Parkinson’s Disease and Alzheimer’s Disease · doi:10.13188/2376-922x.1000003 · Cited by 80
Regulation of MMP-1 expression in response to hypoxia is dependent on the intracellular redox status of metastatic bladder cancer cells
Shin, D. H., Dier, U., Melendez, J. A., & Hempel, N. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.09.001 · Cited by 77

Authors: Pan, Y., Mansfield, K. D., Bertozzi, C. C., Rudenko, V., Chan, D. A., Giaccia, A. J., & Simon, M. C.
Affiliations: Howard Hughes Medical Institute (US)
University of Pennsylvania (US)
Stanford Medicine (US)
Corresponding author: Simon, M. Celeste
ORCID: Mansfield, Kyle D.
Giaccia, Amato J.
Simon, M. Celeste
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2007-02-01
Volume: 27
Issue: 3
Pages: 912-925
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.01223-06
PMC: PMC1800695
OpenAlex: W2105236768
Cited by: 332
References: 59
Citations by year: 2026: 8 · 2025: 7 · 2024: 16 · 2023: 15 · 2022: 15 · 2021: 11 · 2020: 14 · 2019: 18 · 2018: 16 · 2017: 14 · 2016: 25 · 2015: 19 · 2014: 18 · 2013: 22 · 2012: 19
FWCI: 6.53
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
Cancer Research Institute
National Institutes of Health (CA104838)
National Cancer Institute (P01CA104838, CA104838)
Abramson Family Cancer Research Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Keywords: HIF-1α, oxygen-dependent degradation domain, HIF-1α stabilization, cellular redox status, energy metabolism, iron, vitamin C, tricarboxylic acid cycle intermediates, reactive oxygen species, mitochondrial inhibitors, rotenone, myxothiazol, oxygen deprivation, reoxygenation
MeSH terms: Animals, Carcinoma, Renal Cell, Electron Transport, Electrophoresis, Polyacrylamide Gel, Energy Metabolism, Gene Expression Regulation, Humans, Hydrogen Peroxide, Hydroxylation, Mitochondria, Oxidation-Reduction, Proline, Procollagen-Proline Dioxygenase, Recombinant Fusion Proteins, RNA, Messenger, Thermodynamics, Uncoupling Agents, Cell Hypoxia, Molecular Mimicry, Protein Transport, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Multiple Factors Affecting Cellular Redox Status and Energy Metabolism Modulate Hypoxia-Inducible Factor Prolyl Hydroxylase Activity In Vivo and In Vitro

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks