The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production
Open accessAbstract
Mammalian cells increase transcription of genes for adaptation to hypoxia through the stabilization of hypoxia-inducible factor 1α (HIF-1α) protein. How cells transduce hypoxic signals to stabilize the HIF-1α protein remains unresolved. We demonstrate that cells deficient in the complex III subunit cytochrome b, which are respiratory incompetent, increase ROS levels and stabilize the HIF-1α protein during hypoxia. RNA interference of the complex III subunit Rieske iron sulfur protein in the cytochrome b–null cells and treatment of wild-type cells with stigmatellin abolished reactive oxygen species (ROS) generation at the Qo site of complex III. These interventions maintained hydroxylation of HIF-1α protein and prevented stabilization of HIF-1α protein during hypoxia. Antioxidants maintained hydroxylation of HIF-1α protein and prevented stabilization of HIF-1α protein during hypoxia. Exogenous hydrogen peroxide under normoxia prevented hydroxylation of HIF-1α protein and stabilized HIF-1α protein. These results provide genetic and pharmacologic evidence that the Qo site of complex III is required for the transduction of hypoxic signal by releasing ROS to stabilize the HIF-1α protein.
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
Cites
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?
Mitochondria have been proposed to serve as a cellular oxygen sensor, such that in hypoxic conditions, mitochondrial ROS production by complex III leads to stabilization of HIF1α and downstream hypoxic adaptation.
“For example, mitochondria have been proposed to serve as a cellular oxygen sensor, such that in hypoxic conditions, mitochondrial ROS production by complex III leads to the stabilization of HIF1α and downstream hypoxic adaptation (84, 997).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [84]
Mitochondria are a physiologically significant source of ROS with important implications in physiology, not only in cardiovascular disease but in many other conditions like aging.
“Mitochondria are a physiologically significant source of ROS with important implications in physiology, not only in cardiovascular disease but in many other conditions like aging (57, 84, 136, 165, 170, 290, 864, 997).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [84]
Another method that depends on the interaction of O2•− and NO• is the formation of dityrosine from tyrosine by ONOO−.
“Another method that depends on the interaction of O2•− and NO• is the formation of dityrosine from tyrosine by ONOO− (29); Fig. 7 shows an example of the dynamic changes in dityrosine formation in intact hearts during a change in temperature and drug treatment.”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [29]
NO• is not ionized and so is much more membrane permeable and can compete for O2•− with SOD to produce the nonradical ONOO−, which protonates at a low pH to ONOOH, which is highly reactive to tissues.
“NO• is not ionized and so is much more membrane permeable and can compete for O2•− with SOD to produce the nonradical ONOO− (29), which protonates at a low pH to ONOOH, which is highly reactive to tissues.”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [29]
Genetic and pharmacologic interventions that limit ROS production at complex III inhibit the ability of cells to respond to acute hypoxia without limiting their ability to respond to interventions that mimic hypoxia.
“Genetic and pharmacologic interventions that limit ROS production at complex III inhibit the ability of cells to respond to acute hypoxia without limiting their ability to respond to interventions that mimic hypoxia (6, 10, 11, 21, 31).”
Cells expressing a mutant cytochrome b subunit are unable to consume oxygen for oxidative phosphorylation but are able to produce complex III-derived ROS and stabilize HIF during hypoxia.
“Thus, cells that express a mutant cytochrome b subunit are unable to consume oxygen for oxidative phosphorylation, but are able to produce complex III-derived ROS and stabilize HIF during hypoxia 20.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [20]
HIF stabilization afforded by mitochondrial ROS is a result of PHD inhibition.
“HIF stabilization afforded by mitochondrial ROS is a result of PHD inhibition”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [20]
Genetic targeting of the complex III subunit Rieske iron-sulfur protein abolishes ROS formation during hypoxia, preventing activation of downstream signaling effectors.
“Thus, genetic targeting of the complex III subunit Rieske iron-sulfur protein, the protein required for electron transfer from ubiquiol, abolishes ROS formation during hypoxia, preventing the activation of downstream signaling effectors 17, 19, 20.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [20]
The ability of complex III to pump protons or to participate in oxidative phosphorylation is not required for ROS generation at this complex.
“Later work demonstrated that the ability of complex III to pump protons or to participate in oxidative phosphorylation is not required for ROS generation at this complex.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084 · see citing works
Oxyl radicals, redox-sensitive signalling cascades and antioxidants
Genestra, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.04.009 · Cited by 4,930 · see citing works
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 1× · see citing works
“Proline hydroxylation targets the protein for ubiquitination by the von Hippel-Lindau protein (pVHL)/E3 ubiquitin ligase and for subsequent proteasomal degradation (Maxwell et al., 1999; Bruick and McKnight, 2001; Epstein et al., 2001; Ivan et al., 2001; Jaakkola et al., 2001).”
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 · see citing works
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 · see citing works
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · see citing works
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 · see citing works
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 · see citing works
Self-citationGeneration of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria
Turrens, J. F., & Boveris, A. (1980) · Biochemical Journal · doi:10.1042/bj1910421 · Cited by 1,601 · see citing works
Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594 · see citing works
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558 · see citing works
Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · cited 1× · see citing works
“The α subunit is also hydroxylated at an asparagine residue by the enzyme factor inhibiting HIF-1 (FIH-1) under normal oxygen conditions (Mahon et al., 2001; Lando et al., 2002a,b).”
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 · see citing works
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385 · see citing works
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 · see citing works
Giorgio, M., Migliaccio, E., Orsini, F., Paolucci, D., Moroni, M., Contursi, C., Pelliccia, G., Luzi, L., Minucci, S., Marcaccio, M., et al. (2005) · Cell · doi:10.1016/j.cell.2005.05.011 · Cited by 1,176 · see citing works
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 · see citing works
Gao, X., Wu, G., Gu, X., Fu, L., & Mei, C. (2013) · Kidney & Blood Pressure Research · doi:10.1159/000355743 · Cited by 1,036 · see citing works
Mitochondrial transcription factor A regulates mtDNA copy number in mammals
Ekstrand, M. I. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh109 · Cited by 919 · see citing works
HIF-1 and human disease: one highly involved factor
Semenza, G. L. (2000) · Genes & Development · doi:10.1101/gad.14.16.1983 · Cited by 909 · see citing works
Cadenas, E., Boveris, A., Ragan, C. I., & Stoppani, A. O. M. (1977) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(77)90035-2 · Cited by 855 · see citing works
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 · see citing works
Self-citationRedistribution 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 · see citing works
Kushnareva, Y., Murphy, A. N., & Andreyev, A. Y. (2002) · Biochemical Journal · doi:10.1042/bj20021121 · Cited by 677 · see citing works
Role of ubiquinone in the mitochondrial generation of hydrogen peroxide
Boveris, A., Cadenas, E., & Stoppani, A. O. M. (1976) · Biochemical Journal · doi:10.1042/bj1560435 · Cited by 655 · see citing works
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 · see citing works
HAN, D., WILLIAMS, E., & CADENAS, E. (2001) · Biochemical Journal · doi:10.1042/bj3530411 · Cited by 593 · see citing works
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 · see citing works
Lenaz, G. (2001) · IUBMB Life · doi:10.1080/15216540152845957 · Cited by 585 · see citing works
Han, D., WILLIAMS, E., & Cadenas, E. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3530411 · Cited by 516 · see citing works
Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α
Freedman, S. J., Sun, Z., Poy, F., Kung, A. L., Livingston, D. M., Wagner, G., & Eck, M. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082117899 · Cited by 457 · see citing works
The effect of hyperoxia on superoxide production by lung submitochondrial particles
Turrens, J. F., Freeman, B. Α., Levitt, J. G., & Crapo, J. D. (1982) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(82)90518-5 · Cited by 448 · see citing works
Structural basis for Hif-1α/CBP recognition in the cellular hypoxic response
Dames, S. A., Martinez‐Yamout, M. A., Guzman, R. N. D., Dyson, H. J., & Wright, P. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082121399 · Cited by 404 · see citing works
Pan, Y., Mansfield, K. D., Bertozzi, C. C., Rudenko, V., Chan, D. A., Giaccia, A. J., & Simon, M. C. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01223-06 · Cited by 332 · see citing works
Genova, M. L., Ventura, B., Giuliano, G., Bovina, C., Formiggini, G., Castelli, G. P., & Lenaz, G. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02850-2 · Cited by 297 · see citing works
Emerling, B. M., Platanias, L. C., Black, E. V. I., Nebreda, Á. R., Davis, R. J., & Chandel, N. S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.12.4853-4862.2005 · Cited by 257 · see citing works
Self-citationGeneration of Superoxide Anion by Succinate-Cytochromec Reductase from Bovine Heart Mitochondria
Zhang, L., Yu, L. P. C., & Yu, C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.33972 · Cited by 253 · see citing works
Protonmotive pathways and mechanisms in the cytochrome <i>bc</i> <sub>1</sub> complex
Hunte, C., Palsdottir, H., & Trumpower, B. L. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00391-0 · Cited by 216 · see citing works
Paddenberg, R., Ishaq, B., Goldenberg, A., Faulhammer, P., Rose, F., Weissmann, N., Braun-Dullaeus, R. C., & Kummer, W. (2003) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00149.2002 · Cited by 184 · see citing works
Rac1 Activity Is Required for the Activation of Hypoxia-inducible Factor 1
Hirota, K., & Semenza, G. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100677200 · Cited by 169 · see citing works
Turcotte, S., Desrosiers, R. R., & Béliveau, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00427 · Cited by 144 · see citing works
Calcium signaling stimulates translation of HIF‐α during hypoxia
Hui, A. S., Bauer, A. L., Striet, J. B., Schnell, P. O., & Czyzyk-Krzeska, M. (2006) · The FASEB Journal · doi:10.1096/fj.05-5086com · Cited by 136 · see citing works
Sanjuán-Pla, A., Cervera, A. M., Apostolova, N., Garcia-Bou, R., Víctor, V. M., Murphy, M. P., & McCreath, K. J. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.03.088 · Cited by 134 · see citing works
Self-citationMyxothiazol Induces H2O2 Production from Mitochondrial Respiratory Chain
Starkov, A. A., & Fiskum, G. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4409 · Cited by 133 · see citing works
Mitochondrial regulation of oxygen sensing
Bell, E. L., Emerling, B. M., & Chandel, N. S. (2005) · Mitochondrion · doi:10.1016/j.mito.2005.06.005 · Cited by 130 · see citing works
Self-citationDoege, K., Heine, S., Jensen, I., Jelkmann, W., & Metzen, E. (2005) · Blood · doi:10.1182/blood-2005-03-1138 · Cited by 128 · see citing works
Aragonés, J., Jones, D. R., Martı́n-Puig, S., Juan, M. A. S., Alfranca, A., Vidal, F., Vara, A., Mérida, I., & Landázuri, M. O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006180200 · Cited by 113 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
Self-citationROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · see citing works
Self-citationPhysiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632 · see citing works
Self-citationMitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003428107 · Cited by 1,742 · see citing works
Self-citationBirsoy, K., Wang, T., Chen, W. W., Freinkman, E., Abu-Remaileh, M., & Sabatini, D. M. (2015) · Cell · doi:10.1016/j.cell.2015.07.016 · Cited by 1,388 · see citing works
Sena, L. A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D. A., Wang, C.-R., Schumacker, P. T., Licht, J. D., Perlman, H., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.020 · Cited by 1,338 · see citing works
Self-citation13 reasons why the brain is susceptible to oxidative stress
Cobley, J. N., Fiorello, M. L., & Bailey, D. M. (2018) · Redox Biology · doi:10.1016/j.redox.2018.01.008 · Cited by 1,215 · see citing works
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Wheaton, W. W., Weinberg, S. E., Hamanaka, R. B., Soberanes, S., Sullivan, L. B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G. M., Budigner, G. S., et al. (2014) · eLife · doi:10.7554/elife.02242 · Cited by 1,105 · see citing works
Self-citationCycling hypoxia and free radicals regulate angiogenesis and radiotherapy response
Dewhirst, M. W., Cao, Y., & Moeller, B. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2397 · Cited by 1,022 · see citing works
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011 · see citing works
Self-citationThe Two Faces of Reactive Oxygen Species in Cancer
Reczek, C. R., & Chandel, N. S. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-041916-065808 · Cited by 602 · see citing works
“Hypoxia-induced mROS stabilizes the oxygen-sensitive HIF-α subunit by inhibiting PHD2 activity (Bell et al. 2007).”
BackgroundSelf-citationSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Rabinovitch, R. C., Samborska, B., Faubert, B., Ma, E. H., Gravel, S.-P., Andrzejewski, S., Raissi, T. C., Pause, A., St.-Pierre, J., & Jones, R. G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.026 · Cited by 543 · see citing works
Metabolic zonation of the liver: The oxygen gradient revisited
Kietzmann, T. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.012 · Cited by 499 · see citing works
Cellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess
Wellen, K. E., & Thompson, C. B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.004 · Cited by 486 · see citing works
Stowe, D. F., & Camara, A. K. S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2331 · Cited by 471 · see citing works
Movafagh, S., Crook, S., & Vo, K. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25074 · Cited by 469 · see citing works
Bell, E. L., Emerling, B. M., Ricoult, S. J. H., & Guarente, L. (2011) · Oncogene · doi:10.1038/onc.2011.37 · Cited by 440 · see citing works
Self-citationGuzy, R. D., Sharma, B., Bell, E., Chandel, N. S., & Schumacker, P. T. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01338-07 · Cited by 427 · see citing works
Self-citationAn Attempt to Prevent Senescence: A Mitochondrial Approach
Skulachev, V. P., Anisimov, V. N., Antonenko, Y. N., Bakeeva, L. E., Chernyak, B. V., Erichev, V. P., Filenko, O. F., Kalinina, N. I., Kapelko, V. I., Kolosova, N. G., et al. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.12.008 · Cited by 430 · see citing works
Hypoxia. 2. Hypoxia regulates cellular metabolism
Wheaton, W. W., & Chandel, N. S. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00485.2010 · Cited by 426 · see citing works
Self-citationMitochondrial ROS regulation of proliferating cells
Diebold, L., & Chandel, N. S. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.198 · Cited by 391 · see citing works
Self-citationThe mechanism of mitochondrial superoxide production by the cytochrome bc1 complex
Dröse, S., & Brandt, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803236200 · Cited by 386 · see citing works
Superoxide generation by complex III: From mechanistic rationales to functional consequences
Bleier, L., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.12.002 · Cited by 369 · see citing works
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 · see citing works
Self-citationMitochondrial reactive oxygen species regulate hypoxic signaling
Hamanaka, R. B., & Chandel, N. S. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.005 · Cited by 332 · see citing works
Self-citationSIRT3 regulation of mitochondrial oxidative stress
Bause, A. S., & Haigis, M. C. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.007 · Cited by 311 · see citing works
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 · see citing works
Mitochondria and cellular oxygen sensing in the HIF pathway
Taylor, C. T. (2008) · Biochemical Journal · doi:10.1042/bj20071249 · Cited by 298 · see citing works
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 · see citing works
Self-citationSIRT3 regulates progression and development of diseases of aging
McDonnell, E., Peterson, B. S., Bomze, H. M., & Hirschey, M. D. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.06.001 · Cited by 217 · see citing works
Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204 · see citing works
“Hypoxic conditions are considered to raise cytosolic ROS levels and, in this way, induce the activation of HIF (reviewed in [211]) probably in a mitochondrial complex III-dependent manner [212].”
BackgroundProline biosynthesis is a vent for TGFβ‐induced mitochondrial redox stress
Schwörer, S., Berisa, M., Violante, S., Qin, W., Zhu, J., Hendrickson, R. C., Cross, J. R., & Thompson, C. B. (2020) · The EMBO Journal · doi:10.15252/embj.2019103334 · Cited by 193 · see citing works
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 · see citing works
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 · see citing works
Patten, D. A., Lafleur, V. N., Robitaille, G. A., Chan, D. A., Giaccia, A. J., & Richard, D. E. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-01-0025 · Cited by 171 · see citing works
Two phases of disulfide bond formation have differing requirements for oxygen
Koritzinsky, M., Levitin, F., van den Beucken, T., Rumantir, R. A., Harding, N. J., Chu, K. C., Boutros, P. C., Braakman, I., & Wouters, B. G. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201307185 · Cited by 136 · see citing works
Youn, J. Y., Gao, L., & Cai, H. (2012) · Diabetologia · doi:10.1007/s00125-012-2557-6 · Cited by 128 · see citing works
Wang, D., Malo, D., & Hekimi, S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902352 · Cited by 123 · see citing works
Hagen, T. (2012) · Biochemistry Research International · doi:10.1155/2012/436981 · Cited by 100 · see citing works
Serine-dependent redox homeostasis regulates glioblastoma cell survival
Engel, A. L., Lorenz, N. I., Klann, K., Münch, C., Depner, C., Steinbach, J. P., Ronellenfitsch, M. W., & Luger, A.-L. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0794-x · Cited by 85 · see citing works
Montfort, C. V., Matias, N., Fernandez, A., Fucho, R., de la Rosa, L. C., Martinez-Chantar, M. L., Mato, J. M., Machida, K., Tsukamoto, H., Murphy, M. P., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.05.024 · Cited by 83 · see citing works
Self-citationOrr, A. L., Ashok, D., Sarantos, M. R., Shi, T., Hughes, R. E., & Brand, M. D. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.08.170 · Cited by 80 · see citing works
Dröse, S., Hanley, P. J., & Brandt, U. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.01.011 · Cited by 72 · see citing works
Hypoxia and succinate antagonize 2-deoxyglucose effects on glioblastoma
Pistollato, F., Abbadi, S., Rampazzo, E., Viola, G., Puppa, A. D., Cavallini, L., Frasson, C., Persano, L., Panchision, D. M., & Basso, G. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.08.003 · Cited by 51 · see citing works
Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment
Lappano, R., Todd, L. A., Stanic, M., Cai, Q., Maggiolini, M., Marincola, F., & Pietrobon, V. (2022) · Cancers · doi:10.3390/cancers14030539 · Cited by 32 · see citing works
Hypoxia-inducible factor: roles in development, physiology, and disease
Chandel, N. S., & Simon, M. C. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.11 · Cited by 26 · see citing works
Self-citationNys, K., Maes, H., Andrei, G., Snoeck, R., Garmyn, M., & Agostinis, P. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.12.017 · Cited by 22 · see citing works
- Authors
- Bell, E. L., Klimova, T. A., Eisenbart, J., Moraes, C. T., Murphy, M. P., Budinger, G. R. S., & Chandel, N. S.
- Affiliations
- 1Department of Medicine
- University of Miami (US)
- MRC Mitochondrial Biology Unit (GB)
- Northwestern University (US)
- Corresponding author
- Eisenbart, James
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-06-11
- Volume
- 177
- Issue
- 6
- Pages
- 1029-1036
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2064363
- OpenAlex
- W2020498032
- Cited by
- 568
- References
- 52
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 20 · 2023: 22 · 2022: 29 · 2021: 41 · 2020: 45 · 2019: 27 · 2018: 24 · 2017: 37 · 2016: 23 · 2015: 23 · 2014: 34 · 2013: 26 · 2012: 40
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL071643)
- National Cancer Institute (CA123067-01, R01CA123067)
- National Institute of General Medical Sciences (GM60472-07, R01GM060472)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial complex III, Qo site, cytochrome b, Rieske iron-sulfur protein, hypoxia signaling, HIF-1α stabilization, reactive oxygen species, HIF-1α hydroxylation, stigmatellin, antioxidants, hydrogen peroxide, hypoxia-inducible factor
- MeSH terms
- Animals, Electron Transport Complex III, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, Mitochondrial Proteins, Cytochromes b, 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
