Oligomycin-induced bioenergetic adaptation in cancer cells with heterogeneous bioenergetic organization
Open accessAbstract
Cancer cells constantly adapt to oxidative phosphorylation (OXPHOS) suppression resulting from hypoxia or mitochondria defects. Under the OXPHOS suppression, AMP-activated protein kinase (AMPK) regulates global metabolism adjustments, but its activation has been found to be transient. Whether cells can maintain cellular ATP homeostasis and survive beyond the transient AMPK activation is not known. Here, we study the bioenergetic adaptation to the OXPHOS inhibitor oligomycin in a group of cancer cells. We found that oligomycin at 100 ng/ml completely inhibits OXPHOS activity in 1 h and induces various levels of glycolysis gains by 6 h, from which we calculate the bioenergetic organizations of cancer cells. In glycolysis-dominant cells, oligomycin does not induce much energy stress as measured by glycolysis acceleration, ATP imbalance, AMPK activation, AMPK substrate acetyl-CoA carboxylase phosphorylation at Ser(79), and cell growth inhibition. In OXPHOS-dependent LKB1 wild type cells, oligomycin induces 5-8% ATP drops and transient AMPK activation during the initial 1-2 h. After AMPK activation is completed, oligomycin-induced increase of acetyl-CoA carboxylase phosphorylation at Ser(79) is still detected, and cellular ATP is back at preoligomycin treatment levels by sustained elevation of glycolysis. Cell growth, however, is inhibited without an increase in cell death and alteration in cell cycle distribution. In OXPHOS-dependent LKB1-null cells, no AMPK activation by oligomycin is detected, yet cells still show a similar adaptation. We also demonstrate that the adaptation to oligomycin does not invoke activation of hypoxia-induced factor. Our data suggest that cancer cells may grow and survive persistent OXPHOS suppression through an as yet unidentified regulatory mechanism.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
1 μg/mL oligomycin causes a minor nonspecific effect on mitochondrial and cellular function.
“the use of this oligomycin concentration is common in the literature and causes a minor nonspecific effect on mitochondrial and cellular function [15,25,26,27].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [15]
Cultured cancer cells can grow and survive under inhibition of oxidative phosphorylation by oligomycin.
“Notably, cultured cancer cells were able to grow and survive even under the inhibition of oxidative phosphorylation by oligomycin [15].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [15]
1 μg/mL oligomycin (10 times more than 0.1 μg/mL) elicits minor nonspecific effects and is common in the literature.
“However, we used 10 times more oligomycin in our experiments since this oligomycin concentration elicits minor nonspecific effects and it is common in the literature [15,25,26,27].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [15]
Earlier work that blocked glycolysis or oxidative phosphorylation found increased activity of the other pathway.
“These findings confirm previous studies that analyzed inhibition of either glycolysis or OXPHOS, and observed an increase in the activity of the other pathway (Hao et al., 2010; Jose et al., 2011; Birsoy et al., 2014; Dykens et al., 2008).”
From Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis (2019) · cites this paper as Hao et al., 2010
Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · see citing works
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784 · see citing works
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799 · see citing works
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337 · see citing works
p53 Regulates Mitochondrial Respiration
Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M. (2006) · Science · doi:10.1126/science.1126863 · Cited by 1,650 · see citing works
ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis
Ishikawa, K., Takenaga, K., Akimoto, M., Koshikawa, N., Yamaguchi, A., Imanishi, H., Nakada, K., Honma, Y., & Hayashi, J.-I. (2008) · Science · doi:10.1126/science.1156906 · Cited by 1,444 · see citing works
Management of cellular energy by the AMP‐activated protein kinase system
Hardie, D. G., Scott, J. W., Pan, D. A., & Hudson, E. R. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00560-x · Cited by 855 · see citing works
mtDNA mutations increase tumorigenicity in prostate cancer
Petros, J. A., Baumann, A. K., Ruiz‐Pesini, E., Amin, M. B., Sun, C. Q., Hall, J., Lim, S.-D., Issa, M. M., Flanders, W. D., Hosseini, S. H., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408894102 · Cited by 834 · see citing works
Marsin, A.-S., Bertrand, L., Rider, M. H., Deprez, J., Beauloye, C., Vincent, M. F., den Berghe, G. V., Carling, D., & Hue, L. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00742-9 · Cited by 818 · see citing works
5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle.
Kurth-Kraczek, E. J., Hirshman, M. F., Goodyear, L. J., & Winder, W. W. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1667 · Cited by 715 · see citing works
Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR
Russell, R. R., Bergeron, R., Shulman, G. I., & Young, L. H. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.2.h643 · Cited by 553 · see citing works
AMPK and cell proliferation – AMPK as a therapeutic target for atherosclerosis and cancer
Motoshima, H., Goldstein, B. J., Igata, M., & Araki, E. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.108324 · Cited by 529 · see citing works
Almeida, Á., Moncada, S., & Bolaños, J. P. (2003) · Nature Cell Biology · doi:10.1038/ncb1080 · Cited by 481 · see citing works
Regulation of cancer cell metabolism by hypoxia-inducible factor 1
Semenza, G. L. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.11.009 · Cited by 469 · see citing works
The bioenergetic signature of cancer: a marker of tumor progression.
Cuezva, J. M., Krajewska, M., de Heredia, M. L., Krajewski, S., Santamaría, G., Kim, H., Zapata, J. M., Marusawa, H., Chamorro, M., & Reed, J. C. (2002) · PubMed · Cited by 440 · see citing works
Almeida, A., Almeida, J., Bolaños, J. P., & Moncada, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261560998 · Cited by 423 · see citing works
Marsin, A.-S., Bouzin, C., Bertrand, L., & Hue, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205213200 · Cited by 380 · see citing works
Loss of the Mitochondrial Bioenergetic Capacity Underlies the Glucose Avidity of Carcinomas
López‐Ríos, F., Sánchez‐Aragó, M., García-García, E., Ortega, A. D., Berrendero, J. R., Pozo-Rodrı́guez, F., Encuentra, Á. L., Ballestı́n, C., & Cuezva, J. M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1678 · Cited by 178 · see citing works
Samudio, I., Fiegl, M., McQueen, T., Clise-Dwyer, K., & Andreeff, M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0555 · Cited by 168 · see citing works
Oxidative Phosphorylation Enzymes in Normal and Neoplastic Cell Growth
Capuano, F., GUERRIERI, F., & Papa, S. (1997) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1022402915431 · Cited by 78 · see citing works
Metabolic control: A new solution to an old problem
Hardie, D. G. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00744-2 · Cited by 51 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
An inhibitor of oxidative phosphorylation exploits cancer vulnerability
Molina, J. R., Sun, Y., Protopopova, M., Gera, S., Bandi, M., Bristow, C., McAfoos, T., Morlacchi, P., Ackroyd, J., Agip, A.-N. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0052-4 · Cited by 928 · see citing works
Roesch, A., Vultur, A., Bogeski, I., Wang, H., Zimmermann, K. M., Speicher, D., Körbel, C., Laschke, M. W., Gimotty, P. A., Philipp, S. E., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.05.003 · Cited by 670 · see citing works
Liu, Y., Cao, Y., Zhang, W., Bergmeier, S. C., Qian, Y., Akbar, H., Colvin, R. A., Ding, J., Tong, L., Wu, S., et al. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0131 · Cited by 563 · see citing works
Yang, L., Moss, T., Mangala, L. S., Marini, J., Zhao, H., Wahlig, S., Armaiz‐Pena, G., Jiang, D., Achreja, A., Win, J., et al. (2014) · Molecular Systems Biology · doi:10.1002/msb.20134892 · Cited by 326 · see citing works
Elgendy, M., Cirò, M., Hosseini, A., Weiszmann, J., Mazzarella, L., Ferrari, E., Cazzoli, R., Curigliano, G., DeCensi, A., Bonanni, B., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.03.007 · Cited by 299 · see citing works
Davis, R. T., Blake, K., Ma, D., Gabra, M. B. I., Hernandez, G. A., Phung, A. T., Yang, Y., Maurer, D., Lefebvre, A. E. Y. T., Alshetaiwi, H. S., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0477-0 · Cited by 298 · see citing works
Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control
Próchnicki, T., & Latz, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.018 · Cited by 297 · see citing works
Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis
Jeong, H., Kim, S., Hong, B.-J., Lee, C.-J., Kim, Y.-E., Bok, S., Oh, J.-M., Gwak, S.-H., Yoo, M. Y., Lee, M. S., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2545 · Cited by 269 · see citing works
Oxidative phosphorylation in cancer cells
Solaini, G., Sgarbi, G., & Baracca, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.09.003 · Cited by 231 · see citing works
Grasso, D., Zampieri, L. X., Capelôa, T., de Velde, J. A. V., & Sonveaux, P. (2020) · Cell Stress · doi:10.15698/cst2020.06.221 · Cited by 231 · see citing works
Shen, Y.-C., Ou, D., Hsu, C., Lin, K.-L., Chang, C.-Y., Lin, C.-Y., Liu, S., & Cheng, A.-L. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.559 · Cited by 202 · see citing works
A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging
An, H.-W., Li, L., Wang, Y., Wang, Z., Hou, D., Lin, Y.-X., Qiao, S., Wang, M., Yang, C., Cong, Y., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12848-5 · Cited by 193 · see citing works
Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer metabolism
Chevrollier, A., Loiseau, D., Reynier, P., & Stepien, G. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.008 · Cited by 182 · see citing works
C13orf31 (FAMIN) is a central regulator of immunometabolic function
Cader, M. Z., Boroviak, K., Zhang, Q., Assadi, G., Kempster, S. L., Sewell, G. W., Saveljeva, S., Ashcroft, J., Clare, S., Mukhopadhyay, S., et al. (2016) · Nature Immunology · doi:10.1038/ni.3532 · Cited by 168 · see citing works
Nishikawa, T., Bellancé, N., Damm, A., Bing, H., Zhu, Z. H., Handa, K., Yovchev, M. I., Sehgal, V., Moss, T. J., Oertel, M., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.02.014 · Cited by 136 · see citing works
Titanium dioxide nanoparticles impair lung mitochondrial function
Freyre‐Fonseca, V., Delgado‐Buenrostro, N. L., Gutiérrez-Cirlos, E. B., Calderón-Torres, C. M., Cabellos-Avelar, T., Sánchez-Pérez, Y., Pinzón, E., Torres, I., Molina‐Jijón, E., & Zazueta, C. (2011) · Toxicology Letters · doi:10.1016/j.toxlet.2011.01.025 · Cited by 123 · see citing works
Wu, H., Wang, Y., Ying, M., Jin, C., Li, J., & Hu, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00595-3 · Cited by 119 · see citing works
Jeong, S. M., Hwang, S., & Seong, R. H. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.02.023 · Cited by 112 · see citing works
Sirois, I., Aguilar-Mahecha, A., Lafleur, J., Fowler, E., Vu, V., Scriver, M., Buchanan, M., Chabot, C., Ramanathan, A., Balachandran, B., et al. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0264 · Cited by 110 · see citing works
Shiau, J., Chuang, Y.-T., Cheng, Y., Tang, J., Hou, M., Yen, C., & Chang, H. (2022) · Antioxidants · doi:10.3390/antiox11050911 · Cited by 98 · see citing works
Lanning, N. J., Looyenga, B. D., Kauffman, A. L., Niemi, N. M., Sudderth, J., DeBerardinis, R. J., & MacKeigan, J. P. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.065 · Cited by 94 · see citing works
Yamada, K. J., Heim, C. E., Xi, X., Attri, K. S., Wang, D., Zhang, W., Singh, P. K., Bronich, T. K., & Kielian, T. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008354 · Cited by 94 · see citing works
Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis
Gasmi, A., Peana, M., Arshad, M., Butnariu, M., Menzel, A., & Bjørklund, G. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-02974-9 · Cited by 82 · see citing works
Valcarcel‐Ares, M. N., Riveiro-Naveira, R. R., Vaamonde‐García, C., Loureiro, J., Hermida-Carballo, L., Blanco, F. J., & López-Armada, M. J. (2014) · Lara D. Veeken · doi:10.1093/rheumatology/keu016 · Cited by 82 · see citing works
Ruas, J. S., Siqueira-Santos, E. S., Amigo, I., Rodrigues-Silva, E., Kowaltowski, A. J., & Castilho, R. F. (2016) · PLOS ONE · doi:10.1371/journal.pone.0150967 · Cited by 78 · see citing works
Izadifar, Z., Charrez, B., Almeida, M., Robben, S., Pilobello, K. T., van der Graaf-Mas, J., Benz, M., Marquez, S. L., Ferrante, T. C., Shcherbina, K., et al. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116683 · Cited by 77 · see citing works
Gao, C., Shen, Y., Jin, F., Miao, Y., & Qiu, X. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154576 · Cited by 73 · see citing works
Effects of sorafenib on energy metabolism in breast cancer cells: role of AMPK–mTORC1 signaling
Fumarola, C., Caffarra, C., Monica, S. L., Galetti, M., Alfieri, R. R., Cavazzoni, A., Galvani, E., Generali, D., Petronini, P. G., & Bonelli, M. A. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-013-2668-x · Cited by 70 · see citing works
Urra, F. A., Muñoz, F., Córdova-Delgado, M., Ramírez, M. P., Peña-Ahumada, B., Rios, M., Cruz, P., Ahumada-Castro, U., Bustos, G., Silva-Pavez, E., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31367-9 · Cited by 69 · see citing works
Computational Repositioning and Preclinical Validation of Pentamidine for Renal Cell Cancer
Zerbini, L. F., Bhasin, M., de Vasconcellos, J. F., Paccez, J. D., Gu, X., Kung, A. L., & Libermann, T. A. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0750 · Cited by 65 · see citing works
AMPK and GCN2–ATF4 signal the repression of mitochondria in colon cancer cells
Martínez‐Reyes, I., Sánchez‐Aragó, M., & Cuezva, J. M. (2012) · Biochemical Journal · doi:10.1042/bj20111829 · Cited by 64 · see citing works
Willers, I. M., & Cuezva, J. M. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.016 · Cited by 62 · see citing works
Enslin, L. E., Purkait, K., Pozza, M. D., Saubaméa, B., Mesdom, P., Visser, H. G., Gasser, G., & Schutte‐Smith, M. (2023) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.3c00730 · Cited by 61 · see citing works
The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity
Tian, W., Wang, Y., Xu, Y., Guo, X., Wang, B., Sun, L., Liu, L., Cui, F., Zhuang, Q., Bao, X., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.538157 · Cited by 59 · see citing works
Yu, X., Zhang, L., Yang, X., Huang, H., Huang, Z., Shi, L., Zhang, H., & Du, G. (2012) · Molecules · doi:10.3390/molecules170911216 · Cited by 59 · see citing works
Marignac, V. L. M., Smith, S. E., Toban, N., Bazile, M., & Aloyz, R. S. (2013) · Oncotarget · doi:10.18632/oncotarget.1508 · Cited by 54 · see citing works
He, F., Laranjeira, A. B. A., Kong, T., Lin, S., Ashworth, K. J., Liu, A., Lasky, N. M., Fisher, D. A. C., Cox, M. J., Fulbright, M. C., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci172256 · Cited by 49 · see citing works
Xing, Z., Wang, S., & Tran, E. J. (2017) · RNA · doi:10.1261/rna.060335.116 · Cited by 47 · see citing works
José, C., Melser, S., Bénard, G., & Rossignol, R. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4357 · Cited by 46 · see citing works
Ratajczak, K., Łukasiak, A., Grel, H., Dworakowska, B., Jakieła, S., & Stobiecka, M. (2019) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-019-02061-0 · Cited by 46 · see citing works
Kosaisawe, N., Sparta, B., Pargett, M., Teragawa, C., & Albeck, J. G. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.014 · Cited by 46 · see citing works
Distelmaier, F., Valsecchi, F., Liemburg-Apers, D. C., Lebiedzińska, M., Rodenburg, R. J., Heil, S. G., Keijer, J., Fransen, J. A. M., Imamura, H., Danhauser, K., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.12.012 · Cited by 45 · see citing works
Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension
Luo, Y. L., Qi, X., Zhang, Z., Zhang, J., Li, B., Shu, T., Li, X., Hu, H., Li, J., Tang, Q., et al. (2024) · Circulation · doi:10.1161/circulationaha.123.067579 · Cited by 44 · see citing works
Kikuchi, R., Iwai, Y., Tsuji, T., Watanabe, Y., Koyama, N., Yamaguchi, K., Nakamura, H., & Aoshiba, K. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.01.014 · Cited by 44 · see citing works
Regulation of the cell cycle via mitochondrial gene expression and energy metabolism in HeLa cells
Xiong, W., Jiao, Y., Huang, W., Ma, M., Yu, M., Cui, Q., & Tan, D. (2012) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms006 · Cited by 44 · see citing works
mTOR Inhibitor Everolimus in Regulatory T Cell Expansion for Clinical Application in Transplantation
Gedaly, R., Stefano, F. D., Turcios, L. M., Hill, M., Hidalgo, G. E., Mitov, M. I., Alstott, M. C., Butterfield, D. A., Mitchel, H., Hart, J., et al. (2018) · Transplantation · doi:10.1097/tp.0000000000002495 · Cited by 40 · see citing works
Yu, X. M., Fang, B., Liu, Y., Yan, S., Cao, D., Mei, H., Wang, Q., Hu, Y., & Guo, T. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117971 · Cited by 40 · see citing works
Fischer, A., Zhang, P., Ouyang, Y., Sohn, Y. S., Karmi, O., Nechushtai, R., Pikarsky, E., & Willner, I. (2022) · Small · doi:10.1002/smll.202204108 · Cited by 40 · see citing works
Grande, S., Palma, A., Ricci‐Vitiani, L., Luciani, A. M., Buccarelli, M., Biffoni, M., Molinari, A., Calcabrini, A., D’Amore, E., Guidoni, L., et al. (2018) · Stem Cells International · doi:10.1155/2018/3292704 · Cited by 37 · see citing works
Ma, S., Yeom, J., & Lim, Y. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113672 · Cited by 38 · see citing works
Kennedy, C. R., Tilkens, S. B., Guan, H., Garner, J. A., Or, P. M. Y., & Chan, A. M.-L. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.03.020 · Cited by 37 · see citing works
David, J. M., Owens, T. A., Barwe, S. P., & Rajasekaran, A. K. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0445 · Cited by 36 · see citing works
Ruas, J. S., Siqueira‐Santos, E. S., Rodrigues-Silva, E., & Castilho, R. F. (2018) · Scientific Reports · doi:10.1038/s41598-018-35679-8 · Cited by 35 · see citing works
The Many Facets of Tumor Heterogeneity: Is Metabolism Lagging Behind?
Loponte, S., Lovisa, S., Deem, A. K., Carugo, A., & Viale, A. (2019) · Cancers · doi:10.3390/cancers11101574 · Cited by 34 · see citing works
Integration of Mitochondrial Targeting for Molecular Cancer Therapeutics
Marchetti, P., Guerreschi, P., Mortier, L., & Kluza, J. (2015) · International Journal of Cell Biology · doi:10.1155/2015/283145 · Cited by 32 · see citing works
Liu, H., He, Z., Germič, N., Ademi, H., Frangež, Ž., Felser, A., Peng, S., Riether, C., Djonov, V., Nuoffer, J., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0476-5 · Cited by 30 · see citing works
Gammon, S. T., Pisaneschi, F., Bandi, M. L., Smith, M. G., Sun, Y., Rao, Y., Müller, F. L., Wong, F. C., de Groot, J., Ackroyd, J. J., et al. (2019) · Cells · doi:10.3390/cells8121487 · Cited by 31 · see citing works
Huang, C., Hsu, L., Chen, C.-Y., Chang, G., Chang, H.-W., Hung, Y., Liu, K., & Kao, S. (2020) · Cancers · doi:10.3390/cancers12010181 · Cited by 31 · see citing works
Xue, W., Li, X., Li, W., Wang, Y., Jiang, C., Zhou, L., Gao, J., Yu, Y., Shen, Y., & Xu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00856-1 · Cited by 30 · see citing works
Meira, W., Heinrich, T. A., Cadena, S. M. S. C., & Martinez, G. R. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.11.006 · Cited by 29 · see citing works
Advances in metformin‑based metabolic therapy for non‑small cell lung cancer (Review)
Chen, N., Zhou, Y.-S., Wang, L.-C., & Huang, J. (2022) · Oncology Reports · doi:10.3892/or.2022.8266 · Cited by 29 · see citing works
Maeda, Y., Kikuchi, R., Kawagoe, J., Tsuji, T., Koyama, N., Yamaguchi, K., Nakamura, H., & Aoshiba, K. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101093 · Cited by 26 · see citing works
Tau, S. S., Chamberlin, M. D., Yang, H., Marotti, J. D., Muskus, P. C., Roberts, A. M., Carmichael, M. M., Cressey, L. E., Dragnev, C. P. C., Demidenko, E., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-1204 · Cited by 26 · see citing works
Gnocchi, D., Kurzyk, A., Mintrone, A., Lentini, G., Sabbà, C., & Mazzocca, A. (2022) · Biochimie · doi:10.1016/j.biochi.2022.07.016 · Cited by 25 · see citing works
Basu, S., Broxmeyer, H. E., & Hangoc, G. (2013) · Stem Cells and Development · doi:10.1089/scd.2012.0466 · Cited by 25 · see citing works
Yu, Y., Chen, J., Liu, S., & Cheng, D. (2021) · Journal of Materials Chemistry B · doi:10.1039/d1tb01143j · Cited by 23 · see citing works
Serrill, J., Tan, M. H., Fotso, S., Sikorska, J., Kasanah, N., Hau, A. M., McPhail, K. L., Santosa, D. A., Zabriskie, T. M., Mahmud, T., et al. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.11.015 · Cited by 23 · see citing works
Córdova‐Delgado, M., Fuentes-Retamal, S., Palominos, C., López-Torres, C., Guzmán‐Rivera, D., Ramírez‐Rodríguez, O., Araya‐Maturana, R., & Urra, F. A. (2021) · Antioxidants · doi:10.3390/antiox10101618 · Cited by 22 · see citing works
Mercurio, L., Cecchetti, S., Ricci, A. L., Pacella, A., Cigliana, G., Bozzuto, G., Podo, F., Iorio, E., & Carpinelli, G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176108 · Cited by 22 · see citing works
Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells
Lee, D. C., Ta, N. L., Mukherjee, P., Duraj, T., Domin, M. A., Greenwood, B. P., Karmacharya, S., Narain, N. R., Kiebish, M. A., Chinopoulos, C., et al. (2024) · ASN NEURO · doi:10.1080/17590914.2024.2422268 · Cited by 21 · see citing works
Enogieru, A. B., Haylett, W. L., Miller, H. C., van der Westhuizen, F. H., Hiss, D. C., & Ekpo, O. E. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00048-4 · Cited by 21 · see citing works
Ma, D., Hernandez, G. A., Lefebvre, A. E. Y. T., Alshetaiwi, H. S., Blake, K., Dave, K. R., Rauf, M., Williams, J., Davis, R. T., Evans, K. T., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02596-y · Cited by 21 · see citing works
Vrieling, F., van der Zande, H. J. P., Naus, B., Smeehuijzen, L., van Heck, J. I. P., Ignacio, B. J., Bonger, K. M., den Bossche, J. V., Kersten, S., & Stienstra, R. (2024) · Cell Reports Methods · doi:10.1016/j.crmeth.2024.100883 · Cited by 21 · see citing works
Gao, C., Dai, Y., Spezza, P. A., Boasiako, P. A., Tang, A., Rasquinha, G., Zhong, H., Shao, B., Liu, Y., Shi, P. A., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci189801 · Cited by 20 · see citing works
The Suitability of Glioblastoma Cell Lines as Models for Primary Glioblastoma Cell Metabolism
Arthurs, A. L., Keating, D. J., Stringer, B. W., & Conn, S. J. (2020) · Cancers · doi:10.3390/cancers12123722 · Cited by 20 · see citing works
Morrison, B. L., Mullendore, M. E., Stockwin, L. H., Borgel, S. D., Hollingshead, M. G., & Newton, D. L. (2013) · Cancer Medicine · doi:10.1002/cam4.107 · Cited by 18 · see citing works
Takami, G., Ota, M., Nakashima, A., Kaneko, Y. S., Mori, K., Nagatsu, T., & Ota, A. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0457-9 · Cited by 18 · see citing works
Schneegans, S., Löptien, J., Mojzisch, A., Loreth, D., Kretz, O., Raschdorf, C., Hanssen, A., Gocke, A., Siebels, B., Gunasekaran, K., et al. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03020-z · Cited by 18 · see citing works
Monitoring the Effects of Pharmacological Reagents on Mitochondrial Morphology
Fu, D., & Lippincott‐Schwartz, J. (2018) · Current Protocols in Cell Biology · doi:10.1002/cpcb.45 · Cited by 17 · see citing works
Proteomic analysis of a mosquito host cell response to persistent Wolbachia infection
Baldridge, G. D., Higgins, L., Witthuhn, B. A., Markowski, T. W., Baldridge, A. S., Armién, A. G., & Fallon, A. M. (2017) · Research in Microbiology · doi:10.1016/j.resmic.2017.04.005 · Cited by 16 · see citing works
Metabolic regulation of the CCN family genes by glycolysis in chondrocytes
Akashi, S., Nishida, T., El-Seoudi, A., Takigawa, M., Iida, S., & Kubota, S. (2017) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-017-0420-8 · Cited by 16 · see citing works
Basu, S. (2013) · Stem Cell Research · doi:10.1016/j.scr.2013.10.006 · Cited by 14 · see citing works
Grimm, F., Asuaje, A., Jain, A., dos Santos, M. S., Kleinjung, J., Nunes, P. M., Gehrig, S. M., Fets, L., Darici, S., MacRae, J. I., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00065-w · Cited by 14 · see citing works
Mitochondrial dysfunction and epithelial to mesenchymal transition in head neck cancer cell lines
Greier, M. C., Runge, A., Dudás, J., Pider, V., Skvortsova, I., Savic, D., & Riechelmann, H. (2022) · Scientific Reports · doi:10.1038/s41598-022-16829-5 · Cited by 12 · see citing works
A novel acyclic oligomycin A derivative formed via retro-aldol rearrangement of oligomycin A
Lysenkova, L. N., Turchin, K. F., Korolev, A. M., Bykov, E. E., Даниленко, В. Н., Bekker, O. B., Trenin, A. S., Elizarov, S. M., Dezhenkova, L. G., Shtil, A. A., et al. (2012) · The Journal of Antibiotics · doi:10.1038/ja.2012.38 · Cited by 12 · see citing works
Rodrigues-Silva, E., Siqueira‐Santos, E. S., Ruas, J. S., Ignarro, R. S., Figueira, T. R., Rogério, F., & Castilho, R. F. (2017) · Journal of Neuro-Oncology · doi:10.1007/s11060-017-2482-0 · Cited by 12 · see citing works
He, L., He, Z., April-Monn, S., Trefny, M. P., Rougier, J., Salemi, S., Olariu, R., Widmer, H. R., & Simon, H. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0182-8 · Cited by 12 · see citing works
Palma, A., Grande, S., Ricci‐Vitiani, L., Luciani, A. M., Buccarelli, M., Biffoni, M., Dini, V., Cirrone, G. A. P., Ciocca, M., Guidoni, L., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145167 · Cited by 12 · see citing works
Mirveis, Z., Patil, N., & Byrne, H. J. (2024) · FEBS Open Bio · doi:10.1002/2211-5463.13841 · Cited by 9 · see citing works
Shen, C., Yue, X., Dai, L., Wang, J., Li, J., Fang, Q., Zhi, Y., Shi, C., & Li, W. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04385-4 · Cited by 10 · see citing works
Kinetic modelling of the cellular metabolic responses underpinning in vitro glycolysis assays
Patil, N., Mirveis, Z., & Byrne, H. J. (2024) · FEBS Open Bio · doi:10.1002/2211-5463.13765 · Cited by 10 · see citing works
Rizi, B. S., Braasch, K., Salimi, E., Butler, M., Bridges, G. E., & Thomson, D. J. (2014) · Biomicrofluidics · doi:10.1063/1.4903221 · Cited by 9 · see citing works
Su, S., Su, S.-J., Huang, L., & Chiang, Y.-C. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.01.025 · Cited by 9 · see citing works
Scherbakov, A. M., Sorokin, D. V., Omelchuk, O. A., Shchekotikhin, A. E., & Ma, K. (2021) · Biochimie · doi:10.1016/j.biochi.2021.04.003 · Cited by 9 · see citing works
Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Shoshan, M. C. (2013) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201011314030007 · Cited by 9 · see citing works
ATP Restoration by ATP-Deprived Cultured Primary Astrocytes
Karger, G., Willker, J. E., Harders, A. R., Watermann, P., & Dringen, R. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04276-9 · Cited by 8 · see citing works
Das, S., Zea, M. P., Russon, M. P., Xing, Z., Torregrosa‐Allen, S. E., Cervantes, H. E., Harper, H. A., Elzey, B. D., & Tran, E. J. (2025) · iScience · doi:10.1016/j.isci.2025.112219 · Cited by 8 · see citing works
Cardiosphere-Derived Cells Demonstrate Metabolic Flexibility That Is Influenced by Adhesion Status
Afzal, J. M., Chan, A. T., Karakaş, M. F., Woldemichael, K., Vakrou, S., Guan, Y., Rathmell, J. C., Wahl, R. L., Pomper, M. G., Foster, D. B., et al. (2017) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2017.03.016 · Cited by 8 · see citing works
Conserved role of ATP synthase in mammalian cilia
Lin, W., Qiao, C., Hu, J., Wei, Q., & Xu, T. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112520 · Cited by 8 · see citing works
Zhou, Q., Wang, W., He, X., Zhu, X., Shen, Y., Yu, Z., Wang, X., Qi, X., Zhang, X., Fan, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090336 · Cited by 7 · see citing works
- Authors
- Hao, W., Chang, C.-P. B., Tsao, C.-C., & Xu, J.
- Affiliations
- Wyeth (US)
- Corresponding author
- Hao, Wenshan
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 285
- Issue
- 17
- Pages
- 12647-12654
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2857128
- OpenAlex
- W2009114717
- Cited by
- 138
- References
- 24
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 3 · 2014: 12 · 2013: 10 · 2012: 8
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- oligomycin, cancer cells, oxidative phosphorylation inhibition, AMPK, acetyl-CoA carboxylase, glycolysis, ATP homeostasis, LKB1, hypoxia, energy stress, cell growth inhibition
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Acetyl-CoA Carboxylase, Adenosine Triphosphate, Dose-Response Relationship, Drug, Enzyme Activation, Glycolysis, Humans, Mitochondria, Neoplasm Proteins, Neoplasms, Oligomycins, Oxidative Phosphorylation, Phosphorylation, Stress, Physiological, Time Factors, Uncoupling Agents, Cell Hypoxia, Protein Serine-Threonine Kinases, Cell Line, Tumor, AMP-Activated Protein Kinases
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
