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

Farida Korobova1, Vinay Ramabhadran, Henry N Higgs

  • 1Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

Science (New York, N.Y.)
|January 26, 2013
PubMed

Insights

Actin polymerization, driven by inverted formin 2 (INF2) at the endoplasmic reticulum, is essential for mitochondrial fission. This process precedes the action of dynamin-related protein 1 (Drp1), offering insights into Charcot-Marie-Tooth disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial fission is crucial for cellular function.
  • The dynamin-related protein 1 (Drp1) mediates mitochondrial fission.
  • Endoplasmic reticulum (ER) and mitochondrial interactions enhance fission, but the Drp1 recruitment mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of Drp1 recruitment to mitochondria during fission.
  • To investigate the role of actin in mitochondrial fission.
  • To explore the link between INF2, actin, and mitochondrial dynamics.

Main Methods:

  • Mammalian cell culture.
  • Immunofluorescence microscopy to visualize mitochondria, ER, actin, and INF2.
  • Genetic manipulation to study INF2 function and actin polymerization.
  • Biochemical assays to assess protein interactions and cellular processes.

Main Results:

  • Actin polymerization, facilitated by ER-localized inverted formin 2 (INF2), is required for efficient mitochondrial fission.
  • INF2 acts upstream of Drp1 in the fission pathway.
  • Actin filaments accumulate at ER-mitochondria contact sites, mediating initial constriction.
  • INF2-induced actin filaments facilitate Drp1-dependent secondary constriction.

Conclusions:

  • INF2-mediated actin polymerization is a key upstream regulator of mitochondrial fission.
  • This mechanism provides a potential explanation for the cellular defects observed in Charcot-Marie-Tooth disease, which is linked to INF2 mutations.

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