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- Title
MCUR1 is an essential component of mitochondrial Ca<sup>2+</sup> uptake that regulates cellular metabolism.
- Authors
Mallilankaraman, Karthik; Cárdenas, César; Doonan, Patrick J.; Chandramoorthy, Harish C.; Irrinki, Krishna M.; Golenár, Tünde; Csordás, György; Madireddi, Priyanka; Yang, Jun; Müller, Marioly; Miller, Russell; Kolesar, Jill E.; Molgó, Jordi; Kaufman, Brett; Hajnóczky, György; Foskett, J. Kevin; Madesh, Muniswamy
- Abstract
Ca2+ flux across the mitochondrial inner membrane regulates bioenergetics, cytoplasmic Ca2+ signals and activation of cell death pathways. Mitochondrial Ca2+ uptake occurs at regions of close apposition with intracellular Ca2+ release sites, driven by the inner membrane voltage generated by oxidative phosphorylation and mediated by a Ca2+ selective ion channel (MiCa; ref. ) called the uniporter whose complete molecular identity remains unknown. Mitochondrial calcium uniporter (MCU) was recently identified as the likely ion-conducting pore. In addition, MICU1 was identified as a mitochondrial regulator of uniporter-mediated Ca2+ uptake in HeLa cells. Here we identified CCDC90A, hereafter referred to as MCUR1 (mitochondrial calcium uniporter regulator 1), an integral membrane protein required for MCU-dependent mitochondrial Ca2+ uptake. MCUR1 binds to MCU and regulates ruthenium-red-sensitive MCU-dependent Ca2+ uptake. MCUR1 knockdown does not alter MCU localization, but abrogates Ca2+ uptake by energized mitochondria in intact and permeabilized cells. Ablation of MCUR1 disrupts oxidative phosphorylation, lowers cellular ATP and activates AMP kinase-dependent pro-survival autophagy. Thus, MCUR1 is a critical component of a mitochondrial uniporter channel complex required for mitochondrial Ca2+ uptake and maintenance of normal cellular bioenergetics.
- Subjects
MITOCHONDRIA; CELL metabolism; CELLULAR control mechanisms; METABOLISM; BIOENERGETICS; MEMBRANE proteins; CALCIUM in the body
- Publication
Nature Cell Biology, 2012, Vol 14, Issue 12, p1336
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb2622