ADF/cofilin proteins translocate to mitochondria during apoptosis but are not generally required for cell death signaling

Cell Death Differ. 2012 Jun;19(6):958-67. doi: 10.1038/cdd.2011.180. Epub 2011 Dec 2.


Non-muscle cofilin (n-cofilin) is a member of the ADF/cofilin family of actin depolymerizing proteins. Recent studies reported a mitochondrial translocation of n-cofilin during apoptosis. As these studies also revealed impaired cytochrome c release and a block in apoptosis upon small interfering RNA-mediated n-cofilin knockdown, n-cofilin was postulated to be essential for apoptosis induction. To elucidate the general importance of ADF/cofilin activity for apoptosis, we exposed mouse embryonic fibroblasts deficient for n-cofilin, ADF (actin depolymerizing factor), or all ADF/cofilin isoforms to well-characterized apoptosis inducers. Cytochrome c release, caspase-3 activation, and apoptotic chromatin condensation were unchanged in all mutant fibroblasts. Thus, we conclude that ADF/cofilin activity is not generally required for induction or progression of apoptosis in mammalian cells. Interestingly, mitochondrial association of ADF and n-cofilin during apoptosis was preceded by, and dependent on, actin that translocated by a yet unknown mechanism to mitochondria during cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Cofilin 1 / antagonists & inhibitors
  • Cofilin 1 / genetics
  • Cofilin 1 / metabolism*
  • Cytochromes c / metabolism
  • Destrin / antagonists & inhibitors
  • Destrin / genetics
  • Destrin / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Hydrogen Peroxide / toxicity
  • Mice
  • Mitochondria / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Staurosporine / pharmacology


  • Actins
  • Cofilin 1
  • Destrin
  • RNA, Small Interfering
  • Cytochromes c
  • Hydrogen Peroxide
  • Caspase 3
  • Staurosporine