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Mitochondrial reactive oxygen species regulate hypoxic signaling
Open accessAbstract
Physiological hypoxia results in a host of responses that include increased ventilation, constriction of the pulmonary artery, and a cellular transcriptional program that promotes glycolysis, angiogenesis, and erythropoiesis. Mitochondria are the primary consumers of cellular oxygen and have thus been speculated for years to be the site of cellular oxygen sensing. Many of the cellular responses to hypoxia are now known to be mediated by the production of reactive oxygen species at mitochondrial complex III. While the mechanism by which cytosolic oxidant concentration is increased during hypoxia is unknown, the importance of the maintenance of cellular oxygen supply requires further investigation into the role of ROS as hypoxia signaling molecules. The following is a brief overview of the current understanding of the role of mitochondrial-produced ROS in cellular oxygen signaling.
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“These functions are intimately coupled to redox regulation, as HIFs both sense and remodel intracellular ROS levels through effects on mitochondrial activity, antioxidant pathways, and metabolic flux [252,253].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [252]
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Cites
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
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
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
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084
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
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
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251 · cited 1×
“As the hydroxylation reaction requires oxygen, it was widely speculated that PHDs act as the direct oxygen sensors of the HIF pathway [28].”
BackgroundSemenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
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
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Chandel, N. S., McClintock, D. S., Feliciano, C. E., Wood, T. M., Melendez, J. A., Rodriguez, A. M., & Schumacker, P. T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001914200 · Cited by 2,000
Self-citationMitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926
Self-citationHIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
Ohh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T.-Y., Huang, L. E., Pavletich, N., Chau, V., & Kaelin, W. G. (2000) · Nature Cell Biology · doi:10.1038/35017054 · Cited by 1,577
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K. D., Simon, M. C., Hammerling, U., & Schumacker, P. T. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.001 · Cited by 1,545
Tian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351
Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria
Turrens, J. F., Alexandre, A., & Lehninger, A. L. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90293-0 · Cited by 1,214
Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo
Meng, T.-C., Fukada, T., & Tonks, N. K. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00445-8 · Cited by 1,040
Complex iii releases superoxide to both sides of the inner mitochondrial membrane
Muller, F. L., Liu, Y., & Van Remmen, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407715200 · Cited by 1,036
Semenza, G. L., Nejfelt, M. K., Chi, S. M., & Antonarakis, S. E. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5680 · Cited by 990
Weidemann, A., & Johnson, R. S. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.12 · Cited by 941
A Thiol Peroxidase Is an H2O2 Receptor and Redox-Transducer in Gene Activation
Delaunay, A., Pflieger, D., Barrault, M., Vinh, J., & Tolédano, M. B. (2002) · Cell · doi:10.1016/s0092-8674(02)01048-6 · Cited by 902
Redox-based regulation of signal transduction: principles, pitfalls, and promises
Janssen-Heininger, Y. M. W., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., & van der Vliet, A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.011 · Cited by 784
Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
Brunelle, J. K., Bell, E. L., Quesada, N. M., Vercauteren, K., Tiranti, V., Zeviani, M., Scarpulla, R. C., & Chandel, N. S. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.002 · Cited by 763
Self-citationHan, D., Antunes, F., Canali, R., Rettori, D., & Cadenas, E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210269200 · Cited by 711
Redistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1α
Hagen, T., Taylor, C. T., Lam, F., & Moncada, S. (2003) · Science · doi:10.1126/science.1088805 · Cited by 704
Richard, D. E., Berra, E., & Pouysségur, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003325200 · Cited by 635
Mansfield, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T., & Simon, M. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.003 · Cited by 606
JunD Reduces Tumor Angiogenesis by Protecting Cells from Oxidative Stress
Gerald, D., Berra, E., Frapart, Y. M., Chan, D. A., Giaccia, A. J., Mansuy, D., Pouysségur, J., Yaniv, M., & Mechta-Grigoriou, F. (2004) · Cell · doi:10.1016/j.cell.2004.08.025 · Cited by 588
Gu, Y.-Z., Moran, S. M., Hogenesch, J. B., Wartman, L. D., & Bradfield, C. A. (1998) · Europe PMC (PubMed Central) · Cited by 577
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
Self-citationAcute Oxygen-Sensing Mechanisms
Weir, Ε. K., López‐Barneo, J., Buckler, K. J., & Archer, S. L. (2005) · New England Journal of Medicine · doi:10.1056/nejmra050002 · Cited by 489
Ahn, S., & Thiele, D. J. (2003) · Genes & Development · doi:10.1101/gad.1044503 · Cited by 449
Model for Hypoxic Pulmonary Vasoconstriction Involving Mitochondrial Oxygen Sensing
Waypa, G. B., Chandel, N. S., & Schumacker, P. T. (2001) · Circulation Research · doi:10.1161/hh1201.091960 · Cited by 367
Self-citationBiology of hypoxia-inducible factor-2α in development and disease
Patel, S. A., & Simon, M. C. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.17 · Cited by 335
Emerling, B. M., Weinberg, F., Snyder, C., Burgess, Z., Mutlu, G. M., Viollet, B., Budinger, G. R. S., & Chandel, N. S. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.019 · Cited by 330
Self-citationRathore, R., Zheng, Y.-M., Niu, C.-F., Liu, Q.-H., Korde, A., Ho, Y.-S., & Wang, Y.-X. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.06.012 · Cited by 283
Pulmonary Artery NADPH-Oxidase is Activated in Hypoxic Pulmonary Vasoconstriction
Marshall, C., Mamary, A. J., Verhoeven, A. J., & Marshall, B. E. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.15.5.8918370 · Cited by 256
Bell, E. L., Klimova, T. A., Eisenbart, J., Schumacker, P. T., & Chandel, N. S. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02265-06 · Cited by 237
Self-citationWard, J. P. T. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.10.010 · Cited by 224
The Role of Mitochondria in the Regulation of Hypoxia-inducible Factor 1 Expression during Hypoxia
Agani, F. H., Pichiule, P., Chavez, J. C., & LaManna, J. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005643200 · Cited by 208
Waypa, G. B., Guzy, R., Mungai, P. T., Mack, M. M., Marks, J. D., Roe, M. W., & Schumacker, P. T. (2006) · Circulation Research · doi:10.1161/01.res.0000247068.75808.3f · Cited by 191
Erythropoietin: a Model System for Studying Oxygen-Dependent Gene Regulation
Bunn, H. F., Gu, J., Huang, L. E., Park, J., & Zhu, H. (1998) · Journal of Experimental Biology · doi:10.1242/jeb.201.8.1197 · Cited by 187
Hypoxic pulmonary vasoconstriction: mechanisms and controversies
Aaronson, P. I., Robertson, T. P., Knock, G. A., Becker, S., Lewis, T. H. J., Snetkov, V. A., & Ward, J. P. T. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.098855 · Cited by 160
Superoxide anion generation by the cytochrome bc1 complex
Sun, J. L., & Trumpower, B. L. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.028 · Cited by 157
Comellas, A. P., Dada, L. A., Lecuona, E., Pesce, L. M., Chandel, N. S., Quesada, N. M., Budinger, G. R. S., Strous, G. J., Ciechanover, A. J., & Sznajder, J. I. (2006) · Circulation Research · doi:10.1161/01.res.0000222418.99976.1d · Cited by 125
Self-citationHypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries
Liu, J. Q., Sham, J. S. K., Shimoda, L. A., Kuppusamy, P., & Sylvester, J. T. (2003) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00337.2002 · Cited by 105
Wang, Q., Zheng, Y., Dong, L., Ho, Y.-S., Guo, Z., & Wang, Y.-X. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.12.008 · Cited by 103
Hypoxic vasoconstriction in intact lungs: a role for NADPH oxidase-derived H2O2?
Weißmann, N., Tadić, A., Hänze, J., Rose, F., Winterhalder, S., Nollen, M., SCHERMULY, R. T., Ghofrani, H. A., Seeger, W., & Grimminger, F. (2000) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2000.279.4.l683 · Cited by 98
Hydrogen peroxide-induced Ca2+mobilization in pulmonary arterial smooth muscle cells
Lin, M., Yang, X.-R., Cao, Y.-N., & Sham, J. S. K. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00323.2006 · Cited by 85
Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF gene
Grishko, V. I., Solomon, M., Breit, J. F., Killilea, D. W., LeDoux, S. P., Wilson, G. L., & Gillespie, M. N. (2001) · The FASEB Journal · doi:10.1096/fj.00-0755fje · Cited by 80
Mechanism of hypoxic injury to pulmonary artery endothelial cell plasma membranes
Block, E. R., Patel, J. M., & Edwards, D. A. (1989) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1989.257.2.c223 · Cited by 75
The role of the endothelium in hypoxic pulmonary vasoconstriction
Ward, J., & Robertson, T. P. (1995) · Experimental Physiology · doi:10.1113/expphysiol.1995.sp003887 · Cited by 71
Oxygen sensing in hypoxic pulmonary vasoconstriction: using new tools to answer an age‐old question
Waypa, G. B., & Schumacker, P. T. (2007) · Experimental Physiology · doi:10.1113/expphysiol.2007.041236 · Cited by 58
Calcium, mitochondria and oxygen sensing in the pulmonary circulation
Ward, J. P. T., Snetkov, V. A., & Aaronson, P. I. (2004) · Cell Calcium · doi:10.1016/j.ceca.2004.02.017 · Cited by 45
Flagged first, then by citations
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Research works printed but not linked: 1
- Richard, 2000, Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells, J Biol Chem, 275, 26765, 10.1016/S0021-9258(19)61441-9 · DOI
Cited by
Sorted by citations
Lu, X., Naidis, G. V., Laroussi, M., Reuter, S., Graves, D. B., & Ostrikov, K. (2016) · Physics Reports · doi:10.1016/j.physrep.2016.03.003 · Cited by 1,247
Oxygen Sensing, Homeostasis, and Disease
Semenza, G. L. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1011165 · Cited by 1,014
How cancer metabolism is tuned for proliferation and vulnerable to disruption
Schulze, A., & Harris, A. L. (2012) · Nature · doi:10.1038/nature11706 · Cited by 945
SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization
Finley, L. W. S., Carracedo, A., Lee, J., Souza, A., Egia, A., Zhang, J., Teruya-Feldstein, J., Moreira, P. I., Cardoso, S. M., Clish, C. B., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.02.014 · Cited by 782
Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction
Chen, C., Gao, J., Liu, M., Li, S., Xuan, X., Zhang, X., Zhang, X.-Y., Wei, Y., Zhen, C., Jin, J., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479536 · Cited by 782
Metadata
- Authors
- Hamanaka, R. B., & Chandel, N. S.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Chandel, Navdeep S
- Venue
- Current Opinion in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 21
- Issue
- 6
- Pages
- 894-899
- ISSN
- 0955-0674 (ISSN-L)
- PMC
- PMC2787901
- OpenAlex
- W2107708548
- Cited by
- 332
- References
- 58
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 24 · 2023: 24 · 2022: 23 · 2021: 25 · 2020: 23 · 2019: 10 · 2018: 18 · 2017: 20 · 2016: 20 · 2015: 14 · 2014: 20 · 2013: 20 · 2012: 27
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01CA123067-03, RO1GM60472-10)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial reactive oxygen species, hypoxia signaling, cellular oxygen sensing, mitochondrial complex III, glycolysis, angiogenesis, erythropoiesis, pulmonary vasoconstriction
- MeSH terms
- Animals, Hypoxia, Humans, Mitochondria, Models, Biological, Signal Transduction, Reactive Oxygen Species, Basic Helix-Loop-Helix Proteins
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