MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture

  1. Jonathan R Friedman
  2. Arnaud Mourier
  3. Justin Yamada
  4. J Michael McCaffery
  5. Jodi Nunnari  Is a corresponding author
  1. University of California, Davis, United States
  2. Max Planck Institute for Biology of Ageing, Germany
  3. Johns Hopkins University, United States

Abstract

The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data suggest that MICOS subcomplexes independently localize to cristae junctions and are connected via Mic19, which functions to regulate subcomplex distribution, and thus, potentially also cristae junction copy number. MICOS subunits have non-redundant functions as the absence of MICOS subcomplexes results in more severe morphological and respiratory growth defects than deletion of single MICOS subunits or subcomplexes. Mitochondrial defects resulting from MICOS loss are caused by misdistribution of respiratory complexes in the inner membrane. Together, our data are consistent with a model where MICOS, mitochondrial lipids and respiratory complexes coordinately build a functional and correctly shaped mitochondrial inner membrane.

Article and author information

Author details

  1. Jonathan R Friedman

    Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  2. Arnaud Mourier

    Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    No competing interests declared.
  3. Justin Yamada

    Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  4. J Michael McCaffery

    Integrated Imaging Center, Johns Hopkins University, Baltimore, United States
    Competing interests
    No competing interests declared.
  5. Jodi Nunnari

    Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, United States
    For correspondence
    jmnunnari@ucdavis.edu
    Competing interests
    Jodi Nunnari, Reviewing editor, eLife On Scientific Advisory Board of Mitobridge, and declares no financial interest related to this work..

Reviewing Editor

  1. Richard J Youle, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: March 26, 2015
  2. Accepted: April 27, 2015
  3. Accepted Manuscript published: April 28, 2015 (version 1)
  4. Version of Record published: May 18, 2015 (version 2)

Copyright

© 2015, Friedman 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. Jonathan R Friedman
  2. Arnaud Mourier
  3. Justin Yamada
  4. J Michael McCaffery
  5. Jodi Nunnari
(2015)
MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture
eLife 4:e07739.
https://doi.org/10.7554/eLife.07739

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