MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake
By F. Perocchi, Vishal M. Gohil, Hany S. Girgis, X. Bao, J. Mccombs, Amy E. Palmer, Vamsi K. Mootha. Nature, 2010
877 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/9f412a50a5871d6abc6c22919e61064dee0da934
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
Citations in the corpus
- Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics (2012, background): “The Ca2+ uniporter system is apparently a protein complex (27) that will likely have a wide variety of regulatory mechanisms for changing its conductance.”
- MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins (2015, methodology): “0 has been widely used to elucidate the function of uncharacterized genes and pathways (6–9), including reverse genetic screens (8,10) and forward genetic approaches to identify genes underlying rare mitochondrial disorders (11–14).”
- MICU1 is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake That Regulates Cell Survival (2012, neutral): “It was previously speculated that MICU1 might contribute to Ca2+ cooperativity of uniporter-mediated Ca2+ uptake (Perocchi et al., 2010), but our results suggest that the cooperativity is not mediated by MICU1 and resides elsewhere, possibly the MCU channel itself.”