Abstract

The entry of calcium into mitochondria is central to metabolism, inter-organelle communication, and cell life/death decisions. Long-sought transporters involved in mitochondrial calcium influx and efflux have recently been identified. To obtain a unified picture of mitochondrial calcium utilization, a parallel advance in understanding the forms and quantities of mitochondrial calcium stores is needed. We present here the direct 3D visualization of mitochondrial calcium in intact mammalian cells using cryo-scanning transmission electron tomography (CSTET). Amorphous solid granules containing calcium and phosphorus were pervasive in the mitochondrial matrices of a variety of mammalian cell types. Analysis based on quantitative electron scattering revealed that these repositories are equivalent to molar concentrations of dissolved ions. These results demonstrate conclusively that calcium buffering in the mitochondrial matrix in live cells occurs by phase separation, and that solid-phase stores provide a major ion reservoir that can be mobilized for bioenergetics and signaling.

Article and author information

Author details

  1. Sharon Grayer Wolf

    Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    sharon.wolf@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
  2. Yael Mutsafi

    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Tali Dadosh

    Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Tal Ilani

    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Zipora Lansky

    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Ben Horowitz

    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Sarah Rubin

    Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael Elbaum

    Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7915-5512
  9. Deborah Fass

    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    Deborah.Fass@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9418-6069

Funding

European Research Council under the European Union's Seventh Framework Programme, grand number 310649 (310649)

  • Deborah Fass

I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation (1775/12)

  • Deborah Fass

Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science

  • Sharon Grayer Wolf

Israel Science Foundation (1285/14)

  • Michael Elbaum

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

Reviewing Editor

  1. Werner Kühlbrandt, Max Planck Institute of Biophysics, Germany

Version history

  1. Received: June 28, 2017
  2. Accepted: November 3, 2017
  3. Accepted Manuscript published: November 6, 2017 (version 1)
  4. Version of Record published: November 27, 2017 (version 2)

Copyright

© 2017, Wolf 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. Sharon Grayer Wolf
  2. Yael Mutsafi
  3. Tali Dadosh
  4. Tal Ilani
  5. Zipora Lansky
  6. Ben Horowitz
  7. Sarah Rubin
  8. Michael Elbaum
  9. Deborah Fass
(2017)
3D visualization of mitochondrial solid-phase calcium stores in whole cells
eLife 6:e29929.
https://doi.org/10.7554/eLife.29929

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https://doi.org/10.7554/eLife.29929