Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission

J Cell Biol. 2015 Jan 5;208(1):109-23. doi: 10.1083/jcb.201404050. Epub 2014 Dec 29.

Abstract

In addition to established membrane remodeling roles in various cellular locations, actin has recently emerged as a participant in mitochondrial fission. However, the underlying mechanisms of its participation remain largely unknown. We report that transient de novo F-actin assembly on the mitochondria occurs upon induction of mitochondrial fission and F-actin accumulates on the mitochondria without forming detectable submitochondrial foci. Impairing mitochondrial division through Drp1 knockout or inhibition prolonged the time of mitochondrial accumulation of F-actin and also led to abnormal mitochondrial accumulation of the actin regulatory factors cortactin, cofilin, and Arp2/3 complexes, suggesting that disassembly of mitochondrial F-actin depends on Drp1 activity. Furthermore, down-regulation of actin regulatory proteins led to elongation of mitochondria, associated with mitochondrial accumulation of Drp1. In addition, depletion of cortactin inhibited Mfn2 down-regulation- or FCCP-induced mitochondrial fragmentation. These data indicate that the dynamic assembly and disassembly of F-actin on the mitochondria participates in Drp1-mediated mitochondrial fission.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism*
  • Animals
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Cortactin / genetics
  • Cortactin / metabolism
  • Dynamins / genetics
  • Dynamins / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Mitochondrial Dynamics* / drug effects
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism*
  • Mitosis
  • Protein Transport
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • Actin Depolymerizing Factors
  • Actin-Related Protein 2-3 Complex
  • Actins
  • Cortactin
  • Cttn protein, mouse
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • GTP Phosphohydrolases
  • Mfn2 protein, mouse
  • Dnm1l protein, mouse
  • Dynamins