MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 May 18

PMID 27184846

Citations 122

Authors

Dhanendra Tomar

Zhiwei Dong

Santhanam Shanmughapriya

Diana A Koch

Toby Thomas

Nicholas E Hoffman

Shrishiv A Timbalia

Samuel J Goldman

Sarah L Breves

Daniel P Corbally

Neeharika Nemani

Joseph P Fairweather

Allison R Cutri

Xueqian Zhang

Jianliang Song

Fabian Jana

Jianhe Huang

Carlos Barrero

Joseph E Rabinowitz

Timothy S Luongo

Sarah M Schumacher

Michael E Rockman

Alexander Dietrich

Salim Merali

Jeffrey Caplan

Peter Stathopulos

Rexford S Ahima

Joseph Y Cheung

Steven R Houser

Walter J Koch

Vickas Patel

Vishal M Gohil

John W Elrod

Sudarsan Rajan

Muniswamy Madesh

Affiliations

Soon will be listed here.

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.

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