MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics
| Author(s) | Tomar,Dhanendra | |
| Author(s) | Dong,Zhiwei | |
| Author(s) | Shanmughapriya,Santhanam | |
| Author(s) | Koch,Diana A. | |
| Author(s) | Thomas,Toby | |
| Author(s) | Hoffman,Nicholas E. | |
| Author(s) | Timbalia,Shrishiv A. | |
| Author(s) | Goldman,Samuel J. | |
| Author(s) | Breves,Sarah L. | |
| Author(s) | Corbally,Daniel P. | |
| Author(s) | Nemani,Neeharika | |
| Author(s) | Fairweather,Joseph P. | |
| Author(s) | Cutri,Allison R. | |
| Author(s) | Zhang,Xueqian | |
| Author(s) | Song,Jianliang | |
| Author(s) | Jana,Fabian | |
| Author(s) | Huang,Jianhe | |
| Author(s) | Barrero,Carlos | |
| Author(s) | Rabinowitz,Joseph E. | |
| Author(s) | Luongo,Timothy S. | |
| Author(s) | Schumacher,Sarah M. | |
| Author(s) | Rockman,Michael E. | |
| Author(s) | Dietrich,Alexander | |
| Author(s) | Merali,Salim | |
| Author(s) | Caplan,Jeffrey | |
| Author(s) | Stathopulos,Peter | |
| Author(s) | Ahima,Rexford S. | |
| Author(s) | Cheung,Joseph Y. | |
| Author(s) | Houser,Steven R. | |
| Author(s) | Koch,Walter J. | |
| Author(s) | Patel,Vickas | |
| Author(s) | Gohil,Vishal M. | |
| Author(s) | Elrod,John W. | |
| Author(s) | Rajan,Sudarsan | |
| Author(s) | Madesh,Muniswamy | |
| Ordered Author | 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 and Muniswamy Madesh | |
| UD Author | Caplan, Jeffrey Lewis | |
| Date Accessioned | 2017-07-24T18:41:01Z | |
| Date Available | 2017-07-24T18:41:01Z | |
| Copyright Date | 2016 The Author(s) | |
| Publication Date | 5/24/16 | |
| Description | Publisher's PDF | |
| 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 I-MCU 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. | |
| Department | University of Delaware, Delaware Biotechnology Institute, Department of Biological Sciences | |
| Citation | Tomar, D., Dong, Z., Shanmughapriya, S., Koch, D. A., Thomas, T., Hoffman, N. E., Madesh, M. (2016). MCUR1 is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics. Cell Reports, 15(8), 1673-1685. doi:10.1016/j.celrep.2016.04.050 | |
| DOI | 10.1016/j.celrep.2016.04.050 | |
| ISSN | 2211-1247 | |
| URL | http://udspace.udel.edu/handle/19716/21571 | |
| Language | English | |
| Publisher | Cell Press | |
| dc.rights | CC BY 4.0 | |
| dc.source | Cell Reports | |
| dc.source.uri | http://www.sciencedirect.com/science/journal/22111247/15/8?sdc=1 | |
| Title | MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics | |
| Type | Article |
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