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Article Dans Une Revue Nature Cell Biology Année : 2012

MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism.

Résumé

Ca(2+) flux across the mitochondrial inner membrane regulates bioenergetics, cytoplasmic Ca(2+) signals and activation of cell death pathways. Mitochondrial Ca(2+) uptake occurs at regions of close apposition with intracellular Ca(2+) release sites, driven by the inner membrane voltage generated by oxidative phosphorylation and mediated by a Ca(2+) 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 Ca(2+) 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 Ca(2+) uptake. MCUR1 binds to MCU and regulates ruthenium-red-sensitive MCU-dependent Ca(2+) uptake. MCUR1 knockdown does not alter MCU localization, but abrogates Ca(2+) 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 Ca(2+) uptake and maintenance of normal cellular bioenergetics.

Dates et versions

hal-00781179 , version 1 (25-01-2013)

Identifiants

Citer

Karthik Mallilankaraman, César Cárdenas, Patrick J Doonan, Harish C Chandramoorthy, Krishna M Irrinki, et al.. MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism.. Nature Cell Biology, 2012, 14 (12), pp.1336-43. ⟨10.1038/ncb2622⟩. ⟨hal-00781179⟩

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