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

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...

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Bibliographic Details
Published in:Cell death and differentiation 2012-06, Vol.19 (6), p.958-967
Main Authors: Rehklau, K, Gurniak, C B, Conrad, M, Friauf, E, Ott, M, Rust, M B
Format: Article
Language:English
Subjects:
actin
Actins - metabolism
Animals
Apoptosis
Biochemistry
Biomedical and Life Sciences
Caspase 3 - metabolism
Cell Biology
Cell Cycle Analysis
Cell death
Cells, Cultured
cofilin
Cofilin 1 - antagonists & inhibitors
Cofilin 1 - genetics
Cofilin 1 - metabolism
cytochrome c
Cytochromes c - metabolism
Destrin - antagonists & inhibitors
Destrin - genetics
Destrin - metabolism
Fibroblasts - drug effects
Fibroblasts - metabolism
Hydrogen Peroxide - toxicity
Life Sciences
Mice
mitochondria
Mitochondria - metabolism
Original Paper
RNA Interference
RNA, Small Interfering - metabolism
Staurosporine - pharmacology
Stem Cells
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Summary: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.
ISSN:1350-9047
1476-5403
1476-5403
DOI:10.1038/cdd.2011.180