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Elife. 2015 Aug 25;4. doi: 10.7554/eLife.08828.

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

Author information

1
Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States.
2
Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.
3
Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel.
4
Unit on Structural and Chemical Biology of Membrane Proteins, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States.
5
Department of Biochemistry, Geisel School of Medicine, Hanover, United States.

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 inverted formin 2 (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.

KEYWORDS:

actin; cell biology; cytoskeleton; endoplasmic reticulum; human; membranes; mitochondria; mouse; organelles

PMID:
26305500
PMCID:
PMC4574297
DOI:
10.7554/eLife.08828
[Indexed for MEDLINE]
Free PMC Article

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