MICU1 is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake That Regulates Cell Survival
By K. Mallilankaraman, Patrick J. Doonan, C. Cárdenas, H. Chandramoorthy, Marioly Müller, Russell A. Miller, N. Hoffman, R. Gandhirajan, J. Molgó, M. Birnbaum and 4 more. Cell, 2012
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SUMMARY Mitochondrial Ca2+ (Ca2+m) uptake is mediated by an inner membrane Ca2+ channel called the uniporter. Ca2+ uptake is driven by the considerable voltage present across the inner membrane (ΔΨm) generated by proton pumping by the respiratory chain. Mitochondrial matrix Ca2+ concentration is maintained 5–6 orders of magnitude lower than its equilibrium level, but the molecular mechanisms for how this is achieved are not clear. Here we demonstrate that the mitochondrial protein MICU1 is required to preserve normal [Ca2+]m under basal conditions. In its absence, mitochondria become constitutively loaded with Ca2+, triggering excessive reactive oxygen species generation and sensitivity to apoptotic stress. MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca2+ threshold for Ca2+m uptake without affecting the kinetic properties of MCU-mediated Ca2+ uptake. Thus, MICU1 is a gatekeeper of MCU-mediated Ca2+m uptake that is essential to prevent [Ca2+]m overload and associated stress.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/574a090160fa9c85e5b3c32db55b2f2094f3c5b2
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Citations in the corpus
- Neuronal calcium signaling: function and dysfunction (2014, background): “This is an eF-hand protein that acts as MCU gatekeeper by regulating the threshold of MCU channel opening and allowing its cooperative activation [83, 84], Two paralogs of MICU1, namely, MICU2 and MICU3, and eMRe, an essential single transmembrane protein, have been recently identified; it has been ”