The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism
Open accessAbstract
Cancer cells exhibit increased glycolysis for ATP production due, in part, to respiration injury (the Warburg effect). Because ATP generation through glycolysis is less efficient than through mitochondrial respiration, how cancer cells with this metabolic disadvantage can survive the competition with other cells and eventually develop drug resistance is a long-standing paradox. We report that mitochondrial respiration defects lead to activation of the Akt survival pathway through a novel mechanism mediated by NADH. Respiration-deficient cells (ρ-) harboring mitochondrial DNA deletion exhibit dependency on glycolysis, increased NADH, and activation of Akt, leading to drug resistance and survival advantage in hypoxia. Similarly, chemical inhibition of mitochondrial respiration and hypoxia also activates Akt. The increase in NADH caused by respiratory deficiency inactivates PTEN through a redox modification mechanism, leading to Akt activation. These findings provide a novel mechanistic insight into the Warburg effect and explain how metabolic alteration in cancer cells may gain a survival advantage and withstand therapeutic agents.
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Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
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
Kwon, J., Lee, S.-R., Yang, K.-S., Ahn, Y., Kim, Y. J., Stadtman, E. R., & Rhee, S. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407396101 · Cited by 631
Mitochondrial H2O2 Regulates the Angiogenic Phenotype via PTEN Oxidation
Connor, K. M., Subbaram, S., Regan, K. J., Nelson, K. K., Mazurkiewicz, J. E., Bartholomew, P. J., Aplin, A. E., Tai, Y.-T., Aguirre-Ghiso, J., Flores, S. C., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410690200 · Cited by 251
Cited by
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
Self-citationTargeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Sonveaux, P., Végran, F., Schroeder, T., Wergin, M. C., Verrax, J., Rabbani, Z. N., De Saedeleer, C. J., Kennedy, K. M., Diepart, C., Jordan, B. F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36843 · Cited by 1,624
Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets
Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.116 · Cited by 885
Mitochondrial reactive oxygen species and cancer
Sullivan, L. B., & Chandel, N. S. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-17 · Cited by 786
Human mitochondrial DNA: roles of inherited and somatic mutations
Schon, E. A., DiMauro, S., & Hirano, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3275 · Cited by 757
Metadata
- Authors
- Pelicano, H., Xu, R.-H., Du, M., Feng, L., Sasaki, R., Carew, J. S., Hu, Y., Ramdas, L., Hu, L., Keating, M. J., Zhang, W., Plunkett, W., & Huang, P.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2006-12-11
- Volume
- 175
- Issue
- 6
- Pages
- 913-923
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2089393514
- Cited by
- 387
- References
- 4
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Open access
- green
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- Pelicano, H., Xu, R.-H., Du, M., Feng, L., Sasaki, R., Carew, J. S., Hu, Y., Ramdas, L., Hu, L., Keating, M. J., Zhang, W., Plunkett, W., & Huang, P. (2006). Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200512100
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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