Mitochondrial translocation of oxidized cofilin induces caspase-independent necrotic-like programmed cell death of T cells
Oxidative stress leads to T-cell hyporesponsiveness or death. The actin-binding protein cofilin is oxidized during oxidative stress, which provokes a stiff actin cytoskeleton and T-cell hyporesponsiveness. Here, we show that long-term oxidative stress leads to translocation of cofilin into the mitoc...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
22 July 2010
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| In: |
Cell death & disease
Year: 2010, Volume: 1, Issue: 7, Pages: 1-12 |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2010.36 |
| Online Access: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1038/cddis.2010.36 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/cddis201036 
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| Author Notes: | G.H. Wabnitz, C. Goursot, B. Jahraus, H. Kirchgessner, A. Hellwig, M. Klemke, M.H. Konstandin and Y. Samstag |
| Summary: | Oxidative stress leads to T-cell hyporesponsiveness or death. The actin-binding protein cofilin is oxidized during oxidative stress, which provokes a stiff actin cytoskeleton and T-cell hyporesponsiveness. Here, we show that long-term oxidative stress leads to translocation of cofilin into the mitochondria and necrotic-like programmed cell death (PCD) in human T cells. Notably, cofilin mutants that functionally mimic oxidation by a single mutation at oxidation-sensitive cysteins (Cys-39 or Cys-80) predominately localize within the mitochondria. The expression of these mutants alone ultimately leads to necrotic-like PCD in T cells. Accordingly, cofilin knockdown partially protects T cells from the fatal effects of long-term oxidative stress. Thus, we introduce the oxidation and mitochondrial localization of cofilin as the checkpoint for necrotic-like PCD upon oxidative stress as it occurs, for example, in tumor environments. |
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| Item Description: | Gesehen am 19.09.2023 |
| Physical Description: | Online Resource |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2010.36 |