MICU1 Is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake that Regulates Cell Survival
In: Cell, Jg. 151 (2012-10-01), Heft 3, S. 630-644
Online
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Zugriff:
International audience; 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.
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MICU1 Is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake that Regulates Cell Survival
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Autor/in / Beteiligte Person: | Don-On Daniel Mak ; Molgó, Jordi ; Müller, Marioly ; Rajesh Kumar Gandhirajan ; Hoffman, Nicholas E. ; Doonan, Patrick J. ; Chandramoorthy, Harish C. ; Madesh, Muniswamy ; Miller, Russell A. ; Rothberg, Brad S. ; Cárdenas, César ; Mallilankaraman, Karthik ; Birnbaum, Morris J. ; J. Kevin Foskett ; Department of Physiology, University of Pennsylvania ; University of Pennsylvania [Philadelphia] ; Neurobiologie et Développement (N&eD) ; Centre National de la Recherche Scientifique (CNRS) ; Institut de Neurobiologie Alfred Fessard (INAF) ; Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania ; Department of Cell and Developmental Biology, University of Pennsylvania |
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Zeitschrift: | Cell, Jg. 151 (2012-10-01), Heft 3, S. 630-644 |
Veröffentlichung: | Elsevier BV, 2012 |
Medientyp: | unknown |
ISSN: | 0092-8674 (print) ; 1097-4172 (print) |
DOI: | 10.1016/j.cell.2012.10.011 |
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