1. Biochemistry and Chemical Biology

Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex

  1. Ming-Feng Tsai
  2. Charles B Phillips
  3. Matthew Ranaghan
  4. Chen-Wei Tsai
  5. Yujiao Wu
  6. Carole Willliams
  7. Christopher Miller  Is a corresponding author
  1. Brandeis University, United States
https://doi.org/10.7554/eLife.15545
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Cite this article
  1. Ming-Feng Tsai
  2. Charles B Phillips
  3. Matthew Ranaghan
  4. Chen-Wei Tsai
  5. Yujiao Wu
  6. Carole Willliams
  7. Christopher Miller
(2016)
Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex
eLife 5:e15545.
https://doi.org/10.7554/eLife.15545
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Abstract

Mitochondrial Ca2+ uptake, a process crucial for bioenergetics and Ca2+ signaling, is catalyzed by the mitochondrial calcium uniporter. The uniporter is a multi-subunit Ca2+-activated Ca2+ channel, with the Ca2+ pore formed by the MCU protein and Ca2+-dependent activation mediated by MICU subunits. Recently, a mitochondrial inner membrane protein EMRE was identified as a uniporter subunit absolutely required for Ca2+ permeation. However, the molecular mechanism and regulatory purpose of EMRE remain largely unexplored. Here, we determine the transmembrane orientation of EMRE, and show that its known MCU-activating function is mediated by the interaction of transmembrane helices from both proteins. We also reveal a second function of EMRE: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail. This dual functionality of EMRE ensures that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca2+ landscape.

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Author details

  1. Ming-Feng Tsai

    Department of Biochemistry, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Charles B Phillips

    Department of Biochemistry, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Matthew Ranaghan

    Department of Biochemistry, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Chen-Wei Tsai

    Department of Biochemistry, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Yujiao Wu

    Department of Biochemistry, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Carole Willliams

    Department of Biochemistry, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Christopher Miller

    Department of Biochemistry and the Howard Hughes Medical Institute, Brandeis University, Waltham, United States
    For correspondence
    cmiller@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. David E Clapham, Howard Hughes Medical Institute, Boston Children's Hospital, United States

Version history

  1. Received: February 25, 2016
  2. Accepted: April 19, 2016
  3. Accepted Manuscript published: April 21, 2016 (version 1)
  4. Accepted Manuscript updated: May 6, 2016 (version 2)
  5. Version of Record published: June 3, 2016 (version 3)
  6. Version of Record updated: June 6, 2016 (version 4)
  7. Version of Record updated: March 2, 2017 (version 5)

Copyright

© 2016, Tsai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ming-Feng Tsai
  2. Charles B Phillips
  3. Matthew Ranaghan
  4. Chen-Wei Tsai
  5. Yujiao Wu
  6. Carole Willliams
  7. Christopher Miller
(2016)
Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex
eLife 5:e15545.
https://doi.org/10.7554/eLife.15545

Share this article

https://doi.org/10.7554/eLife.15545

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