The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake
Open accessAbstract
Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease.
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Cites
Proteomic analysis of the mouse liver mitochondrial inner membrane
Da Cruz, S., Xenarios, I., Langridge, J., Vilbois, F., Parone, P. A., & Martinou, J.-C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304940200 · Cited by 247
Cited by
A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
De Stefani, D., Raffaello, A., Teardo, E., Szabò, I., & Rizzuto, R. (2011) · Nature · doi:10.1038/nature10230 · Cited by 1,915
Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
Baughman, J. M., Perocchi, F., Girgis, H. S., Plovanich, M., Belcher-Timme, C. A., Sancak, Y., Bao, X. R., Strittmatter, L., Goldberger, O., Bogorad, R. L., et al. (2011) · Nature · doi:10.1038/nature10234 · Cited by 1,906
Self-citationRath, S., Sharma, R., Gupta, R., Ast, T., Chan, C., Durham, T. J., Goodman, R. P., Grabarek, Z., Haas, M. E., Hung, W. H. W., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1011 · Cited by 1,888
Self-citationMitochondria 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
Directed evolution of APEX2 for electron microscopy and proximity labeling
Lam, S. S., Martell, J. D., Kamer, K. J., Deerinck, T. J., Ellisman, M. H., Mootha, V. K., & Ting, A. Y. (2015) · Nature Methods · doi:10.1038/nmeth.3179 · Cited by 1,377
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Metadata
- Authors
- Perocchi, F., Gohil, V. M., Girgis, H. S., Bao, X. R., McCombs, J. E., Palmer, A. E., & Mootha, V. K.
- Venue
- Nature
- Published
- 2010-08-08
- Volume
- 467
- Issue
- 7313
- Pages
- 291-296
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1991055482
- Cited by
- 881
- References
- 1
- FWCI
- 21.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Perocchi, F., Gohil, V. M., Girgis, H. S., Bao, X. R., McCombs, J. E., Palmer, A. E., & Mootha, V. K. (2010). MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake. Nature. https://doi.org/10.1038/nature09358
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