The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
Citations
Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
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
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
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
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
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
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
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
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
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 868
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 853
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 850
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
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
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 543
Almeida, Á., Moncada, S., & Bolaños, J. P. (2003) · Nature Cell Biology · doi:10.1038/ncb1080 · Cited by 481
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
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
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
Marsin, A.-S., Bouzin, C., Bertrand, L., & Hue, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205213200 · Cited by 380
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 181
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
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
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
Research works printed but not linked: 2
- Cuezva, 2002, Cancer Res., 62, 6674
- Russell, 1999, Am. J. Physiol., 277, H643
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
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
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 586
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
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
Metadata
- 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
