1. Cell Biology
Download icon

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
Research Article
  • Cited 137
  • Views 6,778
  • Annotations
Cite this article as: eLife 2015;4:e07739 doi: 10.7554/eLife.07739

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.

Metrics

  • 6,778
    Page views
  • 1,727
    Downloads
  • 137
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Physics of Living Systems
    Clotilde Cadart et al.
    Research Article

    The way proliferating animal cells coordinate the growth of their mass, volume, and other relevant size parameters is a long-standing question in biology. Studies focusing on cell mass have identified patterns of mass growth as a function of time and cell cycle phase, but little is known about volume growth. To address this question, we improved our fluorescence exclusion method of volume measurement (FXm) and obtained 1700 single-cell volume growth trajectories of HeLa cells. We find that, during most of the cell cycle, volume growth is close to exponential and proceeds at a higher rate in S-G2 than in G1. Comparing the data with a mathematical model, we establish that the cell-to-cell variability in volume growth arises from constant-amplitude fluctuations in volume steps rather than fluctuations of the underlying specific growth rate. We hypothesize that such ‘additive noise’ could emerge from the processes that regulate volume adaptation to biophysical cues, such as tension or osmotic pressure.

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Elizabeth J Lawrence et al.
    Research Article Updated

    Sjögren’s syndrome nuclear autoantigen-1 (SSNA1/NA14) is a microtubule-associated protein with important functions in cilia, dividing cells, and developing neurons. However, the direct effects of SSNA1 on microtubules are not known. We employed in vitro reconstitution with purified proteins and TIRF microscopy to investigate the activity of human SSNA1 on dynamic microtubule ends and lattices. Our results show that SSNA1 modulates all parameters of microtubule dynamic instability—slowing down the rates of growth, shrinkage, and catastrophe, and promoting rescue. We find that SSNA1 forms stretches along growing microtubule ends and binds cooperatively to the microtubule lattice. Furthermore, SSNA1 is enriched on microtubule damage sites, occurring both naturally, as well as induced by the microtubule severing enzyme spastin. Finally, SSNA1 binding protects microtubules against spastin’s severing activity. Taken together, our results demonstrate that SSNA1 is both a potent microtubule-stabilizing protein and a novel sensor of microtubule damage; activities that likely underlie SSNA1’s functions on microtubule structures in cells.