Abstract：
:Mitochondrial Ca(2+) (Ca(2+)(m)) uptake is mediated by an inner membrane Ca(2+) channel called the uniporter. Ca(2+) uptake is driven by the considerable voltage present across the inner membrane (ΔΨ(m)) generated by proton pumping by the respiratory chain. Mitochondrial matrix Ca(2+) concentration is maintained five to six 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 [Ca(2+)](m) under basal conditions. In its absence, mitochondria become constitutively loaded with Ca(2+), triggering excessive reactive oxygen species generation and sensitivity to apoptotic stress. MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca(2+) threshold for Ca(2+)(m) uptake without affecting the kinetic properties of MCU-mediated Ca(2+) uptake. Thus, MICU1 is a gatekeeper of MCU-mediated Ca(2+)(m) uptake that is essential to prevent [Ca(2+)](m) overload and associated stress.
journal_name
Celljournal_title
Cellauthors
Mallilankaraman K,Doonan P,Cárdenas C,Chandramoorthy HC,Müller M,Miller R,Hoffman NE,Gandhirajan RK,Molgó J,Birnbaum MJ,Rothberg BS,Mak DO,Foskett JK,Madesh Mdoi
10.1016/j.cell.2012.10.011subject
Has Abstractpub_date
2012-10-26 00:00:00pages
630-44issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(12)01225-1journal_volume
151pub_type
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