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Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis
Open accessAbstract
Significance: TNF receptor-associated protein (TRAP1) is found predominantly in mitochondria. A possible direct impact of TRAP1 on mitochondrial metabolism remains unexplored. We used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1 deficiency promotes increased mitochondrial respiration, fatty acid oxidation, tricarboxylic acid cycle intermediates, ATP and reactive oxygen species, while concomitantly suppressing glucose metabolism. TRAP1 deficiency also results in strikingly enhanced cell motility and invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes.
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Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502
Fang, H.-Y., Hughes, R., Murdoch, C., Coffelt, S. B., Biswas, S. K., Harris, A. L., Johnson, R. S., Imityaz, H. Z., Simon, M. C., Fredlund, E., et al. (2009) · Blood · doi:10.1182/blood-2008-12-195941 · Cited by 319
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Biebl, M. M., & Buchner, J. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034017 · Cited by 304
Yang, Z., Wang, Y., Zhang, Y., He, X., Zhong, C.-Q., Ni, H., Chen, X., Liang, Y., Wu, J., Zhao, S., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-017-0022-y · Cited by 285
Ganapathy-Kanniappan, S. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1556578 · Cited by 216
Metadata
- Authors
- Yoshida, S., Tsutsumi, S., Muhlebach, G., Sourbier, C., Lee, M.-J., Lee, S., Vartholomaiou, E., Tatokoro, M., Beebe, K., Miyajima, N., Mohney, R. P., Chen, Y., Hasumi, H., Xu, W., Fukushima, H., Nakamura, K., Koga, F., Kihara, K., Trepel, J., Picard, D., & Neckers, L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-04-05
- Volume
- 110
- Issue
- 17
- Pages
- E1604-12
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2094143445
- Cited by
- 279
- References
- 2
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yoshida, S., Tsutsumi, S., Muhlebach, G., Sourbier, C., Lee, M.-J., Lee, S., Vartholomaiou, E., Tatokoro, M., Beebe, K., Miyajima, N., Mohney, R. P., Chen, Y., Hasumi, H., Xu, W., Fukushima, H., Nakamura, K., Koga, F., Kihara, K., Trepel, J., . . . Neckers, L. (2013). Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1220659110
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