biostudies-literatureTomar DNIDA NIH HHSNCRR NIH HHSNIDDK NIH HHSNHLBI NIH HHSNIGMS NIH HHS1673-85https://www.ebi.ac.uk/biostudies/studies/S-EPMC4880542biostudies-literatureUnknown15(8)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 comCell reportsMCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics.PMC4880542P01 HL091799R01 HL123966R01 HL086699P20 GM103446S10 RR027327P30 DK019525P01 DA037830R01 HL119306R01 GM111672R01 GM109882Huang JRabinowitz JEAhima RSDong ZCutri ARBarrero CGohil VMLuongo TSRajan SKoch DABreves SLSchumacher SMHouser SRShanmughapriya SMadesh MThomas TCheung JYTimbalia SAGoldman SJStathopulos PJana FTomar DCorbally DPRockman MEElrod JWDietrich AKoch WJPatel VSong JNemani NFairweather JPHoffman NEMerali SZhang XCaplan JfalseMCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics.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 com2016-01-01T00:00:00Z2016 May2025-04-04T02:35:39.433Z2019-03-27T02:14:34ZS-EPMC48805422718484610.1016/j.celrep.2016.04.050