1. Structural Biology and Molecular Biophysics
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Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane

  1. Yifan Ge
  2. Xiaojun Shi
  3. Sivakumar Boopathy
  4. Julie McDonald
  5. Adam W Smith
  6. Luke H Chao  Is a corresponding author
  1. Massachusetts General Hospital, United States
  2. University of Akron, United States
Research Article
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Cite this article as: eLife 2020;9:e50973 doi: 10.7554/eLife.50973

Abstract

Mitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of Opa1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release. However, stoichiometric levels of the processed, short form of Opa1 (s-Opa1) work together with l-Opa1 to mediate efficient and fast membrane pore opening. Additionally, we found that excess levels of s-Opa1 inhibit fusion activity, as seen under conditions of altered proteostasis. These observations describe a mechanism for gating membrane fusion.

Article and author information

Author details

  1. Yifan Ge

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaojun Shi

    Department of Chemistry, University of Akron, Akron, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8060-5880
  3. Sivakumar Boopathy

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Julie McDonald

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3715-9619
  5. Adam W Smith

    Department of Chemistry, University of Akron, Akron, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5216-9017
  6. Luke H Chao

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    For correspondence
    chao@molbio.mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4849-4148

Funding

Charles H Hood Foundation (Child Health Research Award)

  • Luke H Chao

Charles H Hood Foundation (Child Health Research Award)

  • Yifan Ge

National Science Foundation (CHE-1753060)

  • Xiaojun Shi
  • Adam W Smith

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Publication history

  1. Received: August 9, 2019
  2. Accepted: January 10, 2020
  3. Accepted Manuscript published: January 10, 2020 (version 1)

Copyright

© 2020, Ge 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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