@article{54c209b4a7cc4752a91f6261b188d7bb,
title = "MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics",
abstract = "Mitochondrial Ca2+ Uniporter (MCU)-dependent mitochondrial Ca2+ uptake is the primary mechanism for increasing matrix Ca2+ 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 [Ca2+]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 Ca2+-dependent mitochondrial metabolism.",
author = "Dhanendra Tomar and Zhiwei Dong and Santhanam Shanmughapriya and Koch, {Diana A.} and Toby Thomas and Hoffman, {Nicholas E.} and Timbalia, {Shrishiv A.} and Goldman, {Samuel J.} and Breves, {Sarah L.} and Corbally, {Daniel P.} and Neeharika Nemani and Fairweather, {Joseph P.} and Cutri, {Allison R.} and Xueqian Zhang and Jianliang Song and Fabi{\'a}n Ja{\~n}a and Jianhe Huang and Carlos Barrero and Rabinowitz, {Joseph E.} and Luongo, {Timothy S.} and Schumacher, {Sarah M.} and Rockman, {Michael E.} and Alexander Dietrich and Salim Merali and Jeffrey Caplan and Peter Stathopulos and Ahima, {Rexford S.} and Cheung, {Joseph Y.} and Houser, {Steven R.} and Koch, {Walter J.} and Vickas Patel and Gohil, {Vishal M.} and Elrod, {John W.} and Sudarsan Rajan and Muniswamy Madesh",
note = "Funding Information: We thank Chang-Deng Hu for sharing BiFC plasmid constructs. We also thank Jean L. Ross and Shannon Modla for electron microscopy sample preparation and image acquisition. This research was funded by grants from the NIH (R01GM109882, R01HL086699, R01HL119306, and 1S10RR027327 to M.M.; R01GM111672 to V.M.G.; and P01 DA037830, principal investigator, K. Khalili). Z.D. is supported by the China Scholarship Council (no. 201403170252). V.M.G. is supported by a grant (A-1810) from The Welch Foundation. F.J. is supported by FONDECYT postdoctoral fellowship # 3140458. Metabolic profiling was performed by the University of Pennsylvania Diabetes Research Center, Mouse Phenotyping, Physiology and Metabolism Core (NIH grant P30-DK19525). Access to electron microscopy was supported by NIH-NIGMS (P20 GM103446) and the NSF (IIA-1301765). ",
year = "2016",
month = may,
day = "24",
doi = "10.1016/j.celrep.2016.04.050",
language = "English (US)",
volume = "15",
pages = "1673--1685",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}