An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2

Farida Korobova, Vinay Ramabhadran, Henry N. Higgs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

359 Scopus citations

Abstract

Mitochondrial fission is fundamentally important to cellular physiology. The dynamin-related protein Drp1 mediates fission, and interaction between mitochondrion and endoplasmic reticulum (ER) enhances fission. However, the mechanism for Drp1 recruitment to mitochondria is unclear, although previous results implicate actin involvement. Here, we found that actin polymerization through ER-localized inverted formin 2 (INF2) was required for efficient mitochondrial fission in mammalian cells. INF2 functioned upstream of Drp1. Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites. Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows Drp1-driven secondary constriction. Because INF2 mutations can lead to Charcot-Marie-Tooth disease, our results provide a potential cellular mechanism for this disease state.

Original languageEnglish (US)
Pages (from-to)464-467
Number of pages4
JournalScience
Volume339
Issue number6118
DOIs
StatePublished - Jan 25 2013

ASJC Scopus subject areas

  • General

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