1. Cell Biology

A mitochondria-anchored isoform of the actin-nucleating Spire protein regulates mitochondrial division

  1. Uri Manor
  2. Sadie Bartholomew
  3. Gonen Golani
  4. Eric Christenson
  5. Michael Kozlov
  6. Henry Higgs
  7. James Spudich
  8. Jennifer Lippincott-Schwartz  Is a corresponding author
  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States
  2. Stanford University School of Medicine, United States
  3. Tel Aviv University, Israel
  4. Geisel School of Medicine, United States
https://doi.org/10.7554/eLife.08828
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  1. Uri Manor
  2. Sadie Bartholomew
  3. Gonen Golani
  4. Eric Christenson
  5. Michael Kozlov
  6. Henry Higgs
  7. James Spudich
  8. Jennifer Lippincott-Schwartz
(2015)
A mitochondria-anchored isoform of the actin-nucleating Spire protein regulates mitochondrial division
eLife 4:e08828.
https://doi.org/10.7554/eLife.08828
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Abstract

Mitochondrial division, essential for survival in mammals, is enhanced by an inter-organellar process involving ER tubules encircling and constricting mitochondria. The force for constriction is thought to involve actin polymerization by the ER-anchored isoform of the formin protein INF2. Unknown is the mechanism triggering INF2-mediated actin polymerization at ER-mitochondria intersections. We show that a novel isoform of the formin-binding, actin-nucleating protein Spire, Spire1C, localizes to mitochondria and directly links mitochondria to the actin cytoskeleton and the ER. Spire1C binds INF2 and promotes actin assembly on mitochondrial surfaces. Disrupting either Spire1C actin- or formin-binding activities reduces mitochondrial constriction and division. We propose Spire1C cooperates with INF2 to regulate actin assembly at ER-mitochondrial contacts. Simulations support this model's feasibility and demonstrate polymerizing actin filaments can induce mitochondrial constriction. Thus, Spire1C is optimally positioned to serve as a molecular hub that links mitochondria to actin and the ER for regulation of mitochondrial division.

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Author details

  1. Uri Manor

    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.

  2. Sadie Bartholomew

    Department of Biochemistry, Stanford University School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  3. Gonen Golani

    Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    No competing interests declared.

  4. Eric Christenson

    Unit on Structural and Chemical Biology of Membrane Proteins, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    No competing interests declared.

  5. Michael Kozlov

    Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    Michael Kozlov, Reviewing editor, eLife.

  6. Henry Higgs

    Department of Biochemistry, Geisel School of Medicine, Hanover, United States
    Competing interests
    No competing interests declared.

  7. James Spudich

    Department of Biochemistry, Stanford University School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  8. Jennifer Lippincott-Schwartz

    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States
    For correspondence
    lippincj@mail.nih.gov
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Version history

  1. Received: May 19, 2015
  2. Accepted: August 24, 2015
  3. Accepted Manuscript published: August 25, 2015 (version 1)
  4. Accepted Manuscript updated: September 2, 2015 (version 2)
  5. Version of Record published: September 18, 2015 (version 3)

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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  1. Uri Manor
  2. Sadie Bartholomew
  3. Gonen Golani
  4. Eric Christenson
  5. Michael Kozlov
  6. Henry Higgs
  7. James Spudich
  8. Jennifer Lippincott-Schwartz
(2015)
A mitochondria-anchored isoform of the actin-nucleating Spire protein regulates mitochondrial division
eLife 4:e08828.
https://doi.org/10.7554/eLife.08828

Share this article

https://doi.org/10.7554/eLife.08828

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