1. Structural Biology and Molecular Biophysics
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Atomistic simulations indicate the c-subunit ring of the F1Fo ATP synthase is not the mitochondrial permeability transition pore

  1. Wenchang Zhou
  2. Fabrizio Marinelli  Is a corresponding author
  3. Corrine Nief
  4. José D Faraldo-Gómez  Is a corresponding author
  1. National Heart, Lung and Blood Institute, National Institutes of Health, United States
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Cite this article as: eLife 2017;6:e23781 doi: 10.7554/eLife.23781

Abstract

Pathological metabolic conditions such as ischemia induce the rupture of the mitochondrial envelope and the release of pro-apoptotic proteins, leading to cell death. At the onset of this process, the inner mitochondrial membrane becomes depolarized and permeable to osmolytes, due to the opening of a non-selective protein channel of unknown molecular identity. A recent study purports that this channel, referred to as Mitochondrial Permeability Transition Pore (MPTP), is the lumen of the c-subunit ring of the ATP synthase, upon dissociation from the catalytic domain. Here, we examine this claim for two c-rings of different lumen width, through calculations of their ion conductance and selectivity based on all-atom molecular dynamics simulations. We also evaluate the likelihood that this lumen is hydrated rather than empty or blocked by lipid molecules. These calculations demonstrate that the properties of the lumen of a correctly assembled c-ring are inconsistent with those attributed to the MPTP.

Article and author information

Author details

  1. Wenchang Zhou

    Theoretical Molecular Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0397-1032
  2. Fabrizio Marinelli

    Theoretical Molecular Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    fabrizio.marinelli@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  3. Corrine Nief

    Theoretical Molecular Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. José D Faraldo-Gómez

    Theoretical Molecular Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    jose.faraldo@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7224-7676

Funding

National Heart, Lung, and Blood Institute

  • Wenchang Zhou
  • José D Faraldo-Gómez

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

Reviewing Editor

  1. Yibing Shan, DE Shaw Research, United States

Publication history

  1. Received: November 30, 2016
  2. Accepted: February 9, 2017
  3. Accepted Manuscript published: February 10, 2017 (version 1)
  4. Version of Record published: February 23, 2017 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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