p53 Regulates Mitochondrial Respiration
Abstract
The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase (COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism.
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p53 regulates transcription of TIGAR and SCO2, which have key roles in glucose utilization and mitochondrial respiration.
“This link has been strengthened by recent reports that p53 regulates the transcription of two proteins, TP53-induced glycolosis and apoptosis regulator (TIGAR) and the SCO cytochrome oxidase deficient homologue 2 (SCO2), which have key roles in the utilization of glucose and mitochondrial respiration, respectively 83, 84 .”
From The common biology of cancer and ageing (2007) · cites this paper as [84]
Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · see citing works
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · see citing works
Cancer genes and the pathways they control
Vogelstein, B., & Kinzler, K. W. (2004) · Nature Medicine · doi:10.1038/nm1087 · Cited by 4,245 · see citing works
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472 · see citing works
Requirement for p53 and p21 to Sustain G <sub>2</sub> Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803 · see citing works
Self-citationSenescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
p53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459 · see citing works
Akt Stimulates Aerobic Glycolysis in Cancer Cells
Elstrom, R. L., Bauer, D. E., Buzzai, M., Karnauskas, R., Harris, M. H., Plas, D. R., Zhuang, H., Cinalli, R. M., Alavi, A., Rudin, C. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2904 · Cited by 1,454 · see citing works
Calorie restriction, SIRT1 and metabolism: understanding longevity
Bordone, L., & Guarente, L. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1616 · Cited by 1,021 · see citing works
Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.
Wisløff, U., Najjar, S. M., Ellingsen, Ø., Haram, P. M., Swoap, S., Al-Share, Q., Fernström, M., Rezaei, K., Lee, S. J., Koch, L. G., et al. (2005) · Science · doi:10.1126/science.1108177 · Cited by 657 · see citing works
Glycolytic Enzymes Can Modulate Cellular Life Span
Kondoh, H., Lleonart, M. E., Gil, J., Wang, J., Degan, P., Peters, G., Martinez, D., Carnero, A., & Beach, D. (2005) · Cancer Research · doi:10.1158/0008-5472.177.65.1 · Cited by 647 · see citing works
Modulation of mammalian life span by the short isoform of p53
Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M., & Scrable, H. (2004) · Genes & Development · doi:10.1101/gad.1162404 · Cited by 586 · see citing works
Papadopoulou, L. C., Sue, C. M., Davidson, M. M., Tanji, K., Nishino, I., Sadlock, J. E., Krishna, S., Walker, W., Selby, J. M., Glerum, D. M., et al. (1999) · Nature Genetics · doi:10.1038/15513 · Cited by 571 · see citing works
'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally
García‐Cao, I., García‐Cao, M., Martín‐Caballero, J., Criado, L. M., Klatt, P., Flores, J. M., Weill, J., Blasco, M. A., & Serrano, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf595 · Cited by 529 · see citing works
Identification and classification of p53-regulated genes
Yu, J., Zhang, L., Hwang, P. M., Rago, C., Kinzler, K. W., & Vogelstein, B. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14517 · Cited by 452 · see citing works
Self-citationp53: 25 years after its discovery
Hofseth, L. J., Hussain, S. P., & Harris, C. C. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.02.009 · Cited by 431 · see citing works
Akt-dependent transformation: there is more to growth than just surviving
Plas, D. R., & Thompson, C. B. (2005) · Oncogene · doi:10.1038/sj.onc.1209097 · Cited by 427 · see citing works
Hwang, P. M., Bunz, F., Yu, J., Rago, C., Chan, T. A.-T., Murphy, M. P., Kelso, G. F., Smith, R. A. J., Kinzler, K. W., & Vogelstein, B. (2001) · Nature Medicine · doi:10.1038/nm1001-1111 · Cited by 424 · see citing works
Self-citationKim, J.-W., Zeller, K. I., Wang, Y., Jegga, A. G., Aronow, B. J., O'Donnell, K. A., & Dang, C. V. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5923-5936.2004 · Cited by 371 · see citing works
Cytochrome c oxidase deficiency
Shoubridge, E. A. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1378 · Cited by 328 · see citing works
Coordination and communication between the p53 and IGF-1–AKT–TOR signal transduction pathways
Levine, A. J., Feng, Z., Mak, T. W., You, H., & Jin, S. (2006) · Genes & Development · doi:10.1101/gad.1363206 · Cited by 321 · see citing works
Investigating hypoxic tumor physiology through gene expression patterns
Denko, N. C., Fontana, L., Hudson, K. M., Sutphin, P. D., Raychaudhuri, S., Altman, R. B., & Giaccia, A. J. (2003) · Oncogene · doi:10.1038/sj.onc.1206703 · Cited by 305 · see citing works
‘The Metabolism of Tumours’: 70 Years Later
Semenza, G. L., Artemov, D., Bedi, A., Bhujwalla, Z. M., Chiles, K. A., Feldser, D. M., Laughner, E., Ravi, R. K., Simons, J. W., Taghavi, P., et al. (2001) · Novartis Foundation symposium · doi:10.1002/0470868716.ch17 · Cited by 203 · see citing works
Kohli, M. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh009 · Cited by 165 · see citing works
Mitochondrial proteome: Altered cytochrome c oxidase subunit levels in prostate cancer
Herrmann, P. C., Gillespie, J. W., Charboneau, L., et al. (2003) · PROTEOMICS · doi:10.1002/pmic.200300461 · Cited by 152 · see citing works
An adjustable-current swimming pool for the evaluation of endurance capacity of mice
Matsumoto, K., Ishihara, K., Tanaka, K., Inoue, K., & Fushiki, T. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.81.4.1843 · Cited by 141 · see citing works
Mitochondrial impairment in p53-deficient human cancer cells
Zhou, S. (2003) · Mutagenesis · doi:10.1093/mutage/18.3.287 · Cited by 125 · see citing works
Unleashing the power of p53: lessons from mice and men: Figure 1.Preprint
Poyurovsky, M. V., & Prives, C. L. (2006) · Genes & Development · doi:10.1101/gad.1397506 · Cited by 96 · see citing works
Probing p53 biological functions through the use of genetically engineered mouse models
Attardi, L. D., & Donehower, L. A. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.022 · Cited by 85 · see citing works
Stumpferl, S. W., Stephan, O., & Osiewacz, H. D. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.1.200-211.2004 · Cited by 70 · see citing works
Comparison of energy metabolism in human normal and neoplastic (Burkitt's lymphoma) lymphoid cells.
Sariban-Sohraby, S., MAGRATH, I. T., & Balaban, R. S. (1983) · PubMed · Cited by 34 · see citing works
Flagged first, then by citations
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Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744 · see citing works
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · see citing works
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427 · see citing works
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233 · see citing works
Cancer cell metabolism: warburg and beyond
Hsu, P. P., & Sabatini, D. M. (2008) · Cell · doi:10.1016/j.cell.2008.08.021 · Cited by 2,452 · see citing works
Wallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404 · see citing works
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781 · see citing works
Hypoxia, HIF1 and glucose metabolism in the solid tumour
Denko, N. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2468 · Cited by 1,707 · see citing works
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
DeBerardinis, R. J., & Cheng, T. (2010) · Oncogene · doi:10.1038/onc.2009.358 · Cited by 1,365 · see citing works
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Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.019 · Cited by 1,343 · see citing works
Telomere dysfunction induces metabolic and mitochondrial compromise
Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., et al. (2011) · Nature · doi:10.1038/nature09787 · Cited by 1,319 · see citing works
Oxidative stress and cancer: Have we moved forward?
Halliwell, B. (2007) · Biochemical Journal · doi:10.1042/bj20061131 · Cited by 1,302 · see citing works
The Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes
Levine, A. J., & Puzio-Kuter, A. M. (2010) · Science · doi:10.1126/science.1193494 · Cited by 1,243 · see citing works
Anoikis molecular pathways and its role in cancer progression
Paoli, P., Giannoni, E., & Chiarugi, P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.026 · Cited by 1,160 · see citing works
Tumor suppressors and cell metabolism: a recipe for cancer growth
Jones, R. G., & Thompson, C. B. (2009) · Genes & Development · doi:10.1101/gad.1756509 · Cited by 1,085 · see citing works
P53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080 · see citing works
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007 · see citing works
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Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971 · see citing works
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DeBerardinis, R. J., Sayed, N., Ditsworth, D., & Thompson, C. B. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.02.003 · Cited by 1,018 · see citing works
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016 · see citing works
The common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988 · see citing works
Vousden, K. H., & Ryan, K. M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2715 · Cited by 959 · see citing works
Glucose Deprivation Contributes to the Development of <i>KRAS</i> Pathway Mutations in Tumor Cells
Yun, J., Rago, C., Cheong, I., Pagliarini, R., Angenendt, P., Rajagopalan, H., Schmidt, K., Willson, J. K. V., Markowitz, S., Zhou, S., et al. (2009) · Science · doi:10.1126/science.1174229 · Cited by 914 · see citing works
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885 · see citing works
Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?
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Hu, W., Zhang, C., Wu, R., Sun, Y., Levine, A., & Feng, Z. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001006107 · Cited by 862 · see citing works
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Haq, R., Shoag, J., Andreu-Perez, P., Yokoyama, S., Edelman, H., Rowe, G. C., Frederick, D. T., Hurley, A. D., Nellore, A., Kung, A. L., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.003 · Cited by 818 · see citing works
Stressing the role of FoxO proteins in lifespan and disease
van der Horst, A., & Burgering, B. M. T. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2190 · Cited by 759 · see citing works
Hypoxia and Metabolic Adaptation of Cancer Cells
Eales, K. L., Hollinshead, K. E. R., & Tennant, D. A. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.50 · Cited by 724 · see citing works
Suzuki, S., Tanaka, T., Poyurovsky, M. V., Nagano, H., Mayama, T., Ohkubo, S., Lokshin, M., Hosokawa, H., Nakayama, T., Suzuki, Y., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002459107 · Cited by 705 · see citing works
Kurhanewicz, J., Vigneron, D. B., Brindle, K., Chekmenev, E. Y., Comment, A., Cunningham, C. H., DeBerardinis, R. J., Green, G. G., Leach, M. O., Rajan, S. S., et al. (2011) · Neoplasia · doi:10.1593/neo.101102 · Cited by 681 · see citing works
The expanding universe of p53 targets
Menendez, D., Inga, A., & Resnick, M. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2730 · Cited by 568 · see citing works
The role of nuclear lamin B1 in cell proliferation and senescence
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Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging
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Shock, L. S., Thakkar, P. V., Peterson, E. J., Moran, R. G., & Taylor, S. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012311108 · Cited by 555 · see citing works
Raez, L. E., Papadopoulos, K., Ricart, A. D., Chiorean, E. G., DiPaola, R. S., Stein, M. N., Rocha Lima, C. M., Schlesselman, J. J., Tolba, K., Langmuir, V. K., et al. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-012-2045-1 · Cited by 543 · see citing works
Hoshino, A., Mita, Y., Okawa, Y., Ariyoshi, M., Iwai-Kanai, E., Ueyama, T., Ikeda, K., Ogata, T., & Matoba, S. (2013) · Nature Communications · doi:10.1038/ncomms3308 · Cited by 536 · see citing works
Self-citationCellular and molecular biology of aging endothelial cells
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Choosing between glycolysis and oxidative phosphorylation: a tumor’s dilemma?
Jose, C., Bellance, N., & Rossignol, R. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.012 · Cited by 518 · see citing works
Oncogenic K‐Ras decouples glucose and glutamine metabolism to support cancer cell growth
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Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities
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From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence
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Tumour-associated mutant p53 drives the Warburg effect
Zhang, C., Liu, J., Liang, Y., Wu, R., Zhao, Y., Hong, X., Lin, M., Yu, H., Liu, L., Levine, A. J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3935 · Cited by 434 · see citing works
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AMP-activated protein kinase and its downstream transcriptional pathways
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Mitochondrial membrane permeabilization in neuronal injury
Galluzzi, L., Blomgren, K., & Kroemer, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2665 · Cited by 418 · see citing works
Cancer metabolism: current perspectives and future directions
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Pharmacological approaches to restore mitochondrial function
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Oxygen, a source of life and stress
Brahimi-Horn, M. C., & Pouysségur, J. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.06.018 · Cited by 383 · see citing works
Revving the Engine: Signal Transduction Fuels T Cell Activation
Jones, R. G., & Thompson, C. B. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.008 · Cited by 349 · see citing works
Hypoxia signalling controls metabolic demand
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DNA damage response and metabolic disease
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The Warburg effect is genetically determined in inherited pheochromocytomas
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Granata, C., Oliveira, R. S. F., Little, J. P., Renner, K., & Bishop, D. J. (2016) · The FASEB Journal · doi:10.1096/fj.15-276907 · Cited by 215 · see citing works
Control of glutamine metabolism by the tumor suppressor Rb
Reynolds, M. R., Lane, A. N., Robertson, B., Kemp, S., Liu, Y., Hill, B. G., Dean, D. C., & Clem, B. F. (2014) · Oncogene · doi:10.1038/onc.2012.635 · Cited by 216 · see citing works
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Molecular bases of progeroid syndromes
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Metabolic changes in cancer: beyond the Warburg effect
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Ljubicic, V., Joseph, A.-M., Saleem, A., Uguccioni, G., Collu-Marchese, M., Lai, R. Y. J., Nguyen, L. M.-D., & Hood, D. A. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.031 · Cited by 167 · see citing works
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Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · see citing works
Kaelin, W. G. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010975 · Cited by 161 · see citing works
The role of tumor suppressor p53 in the antioxidant defense and metabolism
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Calcium signaling alterations, oxidative stress, and autophagy in aging
Ureshino, R. P., Rocha, K. K., Lopes, G. S., Bincoletto, C., & Smaili, S. S. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5777 · Cited by 143 · see citing works
Bartlett, J. D., Louhelainen, J., Iqbal, Z., Cochran, A. J., Gibala, M. J., Gregson, W., Close, G. L., Drust, B., & Morton, J. P. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00498.2012 · Cited by 147 · see citing works
Hao, W., Chang, C.-P. B., Tsao, C.-C., & Xu, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.084194 · Cited by 138 · see citing works
CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation
Burns, D. M., & Richter, J. D. (2008) · Genes & Development · doi:10.1101/gad.1697808 · Cited by 134 · see citing works
Obre, E., & Rossignol, R. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.12.008 · Cited by 137 · see citing works
Glucose metabolism in mammalian cell culture: new insights for tweaking vintage pathways
Mulukutla, B. C., Khan, S., Lange, A., & Hu, W.-S. (2010) · Trends in biotechnology · doi:10.1016/j.tibtech.2010.06.005 · Cited by 132 · see citing works
Forini, F., Kusmic, C., Nicolini, G., Mariani, L., Zucchi, R., Matteucci, M., Iervasi, G., & Pitto, L. (2014) · Endocrinology · doi:10.1210/en.2014-1106 · Cited by 132 · see citing works
Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities
Kollareddy, M., Dimitrova, E., Vallabhaneni, K. C., Chan, A., Le, T., Chauhan, K. M., Carrero, Z. I., Ramakrishnan, G., Watabe, K., Haupt, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms8389 · Cited by 127 · see citing works
A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome
Morris, G., & Maes, M. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-012-9324-8 · Cited by 117 · see citing works
Metabolic reprogramming of the tumour microenvironment
Xing, Y., Zhao, S., Zhou, B. P., & Mi, J. (2015) · The FEBS Journal · doi:10.1111/febs.13402 · Cited by 108 · see citing works
Metabolic dysregulation in monogenic disorders and cancer — finding method in madness
Erez, A., & DeBerardinis, R. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3949 · Cited by 105 · see citing works
p53 and mitochondrial dysfunction: novel insight of neurodegenerative diseases
Dai, C.-Q., Luo, T.-T., Luo, S.-C., Wang, J.-Q., Wang, S.-M., Bai, Y.-H., Yang, Y.-L., & Wang, Y.-Y. (2016) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-016-9669-5 · Cited by 93 · see citing works
Böhlig, L., Friedrich, M., & Engeland, K. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq796 · Cited by 85 · see citing works
NFκB/p53 crosstalk—a promising new therapeutic target
Schneider, G., & Krämer, O. H. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2010.10.003 · Cited by 87 · see citing works
Regulation of Metabolic Activity by p53
Flöter, J., Kaymak, I., & Schulze, A. (2017) · Metabolites · doi:10.3390/metabo7020021 · Cited by 81 · see citing works
The mitochondrial genome in aging and senescence
Lauri, A., Pompilio, G., & Capogrossi, M. C. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.001 · Cited by 80 · see citing works
Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function
Lieber, C. S., Leo, M. A., Wang, X., & DeCarli, L. M. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.06.006 · Cited by 71 · see citing works
Hawley, J. A., & Morton, J. P. (2014) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12246 · Cited by 70 · see citing works
CerS6 Is a Novel Transcriptional Target of p53 Protein Activated by Non-genotoxic Stress
Fekry, B., Jeffries, K. A., Esmaeilniakooshkghazi, A., Ogretmen, B., Krupenko, S. A., & Krupenko, N. I. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.716902 · Cited by 59 · see citing works
Wang, S.-J., Yu, G., Jiang, L., Li, T., Lin, Q., Tang, Y., & Gu, W. (2013) · Cell Cycle · doi:10.4161/cc.23597 · Cited by 54 · see citing works
Metabolic alterations accompanying oncogene-induced senescence
Aird, K. M., & Zhang, R. (2014) · Molecular & Cellular Oncology · doi:10.4161/23723548.2014.963481 · Cited by 39 · see citing works
Differential response to exercise in claudin-low breast cancer
Glass, O. K., Bowie, M., Fuller, J., Darr, D., Usary, J., Boss, K., Choudhury, K. R., Liu, X., Zhang, Z., Locasale, J. W., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21054 · Cited by 32 · see citing works
McCubrey, J. A., Meher, A. K., Akula, S. M., Abrams, S. L., Steelman, L. S., LaHair, M. M., Franklin, R. A., Martelli, A. M., Ratti, S., Cocco, L., et al. (2022) · Aging · doi:10.18632/aging.204038 · Cited by 12 · see citing works
Interleukin-1α associates with the tumor suppressor p53 following DNA damage
Novak, J., Zamostna, B., Vopalensky, V., Buryskova, M., Burysek, L., Doleckova, D., & Pospisek, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-63779-x · Cited by 3 · see citing works
- Authors
- Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Hwang, Paul M.
- ORCID
- Venue
- Science
- Published
- 2006-06-16
- Volume
- 312
- Issue
- 5780
- Pages
- 1650-1653
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2062515127
- Semantic Scholar
- 1bbfede2deca0eca860c7169c013b35f491a8c7a
- Cited by
- 1,650
- References
- 31
- Citations by year
- 2026: 25 · 2025: 28 · 2024: 41 · 2023: 44 · 2022: 60 · 2021: 73 · 2020: 91 · 2019: 61 · 2018: 81 · 2017: 72 · 2016: 80 · 2015: 95 · 2014: 122 · 2013: 123 · 2012: 129
- FWCI
- 38.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- p53, mitochondrial respiration, Warburg effect, glycolysis, SCO2, cytochrome c oxidase, cancer metabolism, tumor energy metabolism, p53-deficient cells, aging
- MeSH terms
- Adenosine Triphosphate, Animals, Carrier Proteins, Cell Survival, Electron Transport Complex IV, Glycolysis, Humans, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Mitochondria, Liver, Mutation, Oxygen Consumption, Proteins, Recombination, Genetic, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Molecular Chaperones, Cell Respiration, Mitochondrial Proteins, RNA, Small Interfering, Cell Line, Tumor, Mice
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