title: ADF/cofilin proteins translocate to mitochondria during apoptosis but are not generally required for cell death signaling.
abstract: 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.
authors.affiliation: Neurobiology/Neurophysiology Group, Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Rehklau
authors.forename: C B
authors.initials: CB
authors.lastname: Gurniak
authors.forename: M
authors.initials: M
authors.lastname: Conrad
authors.forename: E
authors.initials: E
authors.lastname: Friauf
authors.forename: M
authors.initials: M
authors.lastname: Ott
authors.forename: M B
authors.initials: MB
authors.lastname: Rust
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D051345:Destrin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D000199:Actins; D051338:Cofilin 1; D051345:Destrin; D034741:RNA, Small Interfering; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D053148:Caspase 3; D019311:Staurosporine