| Literature DB >> 27184846 |
Dhanendra Tomar1, Zhiwei Dong2, Santhanam Shanmughapriya1, Diana A Koch3, Toby Thomas1, Nicholas E Hoffman1, Shrishiv A Timbalia4, Samuel J Goldman1, Sarah L Breves1, Daniel P Corbally1, Neeharika Nemani1, Joseph P Fairweather1, Allison R Cutri1, Xueqian Zhang5, Jianliang Song5, Fabián Jaña1, Jianhe Huang6, Carlos Barrero7, Joseph E Rabinowitz5, Timothy S Luongo5, Sarah M Schumacher5, Michael E Rockman1, Alexander Dietrich8, Salim Merali7, Jeffrey Caplan9, Peter Stathopulos10, Rexford S Ahima11, Joseph Y Cheung5, Steven R Houser6, Walter J Koch5, Vickas Patel6, Vishal M Gohil4, John W Elrod5, Sudarsan Rajan1, Muniswamy Madesh12.
Abstract
Mitochondrial Ca(2+) Uniporter (MCU)-dependent mitochondrial Ca(2+) uptake is the primary mechanism for increasing matrix Ca(2+) in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1) have severely impaired [Ca(2+)]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca(2+)-dependent mitochondrial metabolism.Entities:
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Year: 2016 PMID： 27184846 PMCID： PMC4880542 DOI： 10.1016/j.celrep.2016.04.050
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423