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The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter
Open accessAbstract
Mitochondrial calcium has been postulated to regulate a wide range of processes from bioenergetics to cell death. Here, we characterize a mouse model that lacks expression of the recently discovered mitochondrial calcium uniporter (MCU). Mitochondria derived from MCU−/− mice have no apparent capacity to rapidly uptake calcium. Whereas basal metabolism seems unaffected, the skeletal muscle of MCU−/− mice exhibited alterations in the phosphorylation and activity of pyruvate dehydrogenase. In addition, MCU−/− mice exhibited marked impairment in their ability to perform strenuous work. We further show that mitochondria from MCU−/− mice lacked evidence for calcium-induced permeability transition pore (PTP) opening. The lack of PTP opening does not seem to protect MCU−/− cells and tissues from cell death, although MCU−/− hearts fail to respond to the PTP inhibitor cyclosporin A. Taken together, these results clarify how acute alterations in mitochondrial matrix calcium can regulate mammalian physiology.
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Cites
Myocardial ischemia-reperfusion injury: a neglected therapeutic target
Hausenloy, D. J., & Yellon, D. M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62874 · Cited by 2,357
Mitochondria as sensors and regulators of calcium signalling
Rizzuto, R., De Stefani, D., Raffaello, A., & Mammucari, C. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3412 · Cited by 1,781
Mechanisms by which mitochondria transport calcium
Gunter, T. E., & Pfeiffer, D. R. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.258.5.c755 · Cited by 1,640
Bmi1 regulates mitochondrial function and the DNA damage response pathway
Liu, J., Cao, L., Chen, J., Song, S., Lee, I. H., Quijano, C., Liu, H., Keyvanfar, K., Chen, H., Cao, L.-Y., et al. (2009) · Nature · doi:10.1038/nature08040 · Cited by 474
Self-citationSun, J., Morgan, M., Shen, R.-F., Steenbergen, C., & Murphy, E. (2007) · Circulation Research · doi:10.1161/circresaha.107.155879 · Cited by 367
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Cited by
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Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002
The machineries, regulation and cellular functions of mitochondrial calcium
Giorgi, C., Marchi, S., & Pinton, P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0052-8 · Cited by 941
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724
Enjoy the Trip: Calcium in Mitochondria Back and Forth
De Stefani, D., Rizzuto, R., & Pozzan, T. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034216 · Cited by 423
Mitochondrial calcium exchange in physiology and disease
Garbincius, J. F., & Elrod, J. W. (2022) · Physiological Reviews · doi:10.1152/physrev.00041.2020 · Cited by 412
Metadata
- Authors
- Pan, X., Liu, J., Nguyen, T., Liu, C., Sun, J., Teng, Y., Fergusson, M. M., Rovira, I. I., Allen, M., Springer, D. A., Aponte, A. M., Gucek, M., Balaban, R. S., Murphy, E., & Finkel, T.
- Venue
- Nature Cell Biology
- Published
- 2013-11-10
- Volume
- 15
- Issue
- 12
- Pages
- 1464-1472
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2005641666
- Cited by
- 653
- References
- 5
- FWCI
- 22.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Pan, X., Liu, J., Nguyen, T., Liu, C., Sun, J., Teng, Y., Fergusson, M. M., Rovira, I. I., Allen, M., Springer, D. A., Aponte, A. M., Gucek, M., Balaban, R. S., Murphy, E., & Finkel, T. (2013). The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nature Cell Biology. https://doi.org/10.1038/ncb2868
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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