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Norway

PMID:27184846  

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

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 | Fabián Jaña | 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
Cell reports | 2016

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.

Pubmed ID: 27184846

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM111672
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL119306
  • Agency: NIDA NIH HHS, United States
    Id: P01 DA037830
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM109882
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM103446
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR027327
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL123966
  • Agency: NHLBI NIH HHS, United States
    Id: P01 HL091799
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK019525
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL086699

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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