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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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Hauptverfasser: Wabnitz, Guido H. (VerfasserIn) , Goursot, Catherine (VerfasserIn) , Jahraus, Beate (VerfasserIn) , Kirchgessner, Henning (VerfasserIn) , Hellwig, Andrea (VerfasserIn) , Klemke, Martin (VerfasserIn) , Konstandin, Mathias (VerfasserIn) , Samstag, Yvonne (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 22 July 2010
In: Cell death & disease
Year: 2010, Jahrgang: 1, Heft: 7, Pages: 1-12
ISSN:2041-4889
DOI:10.1038/cddis.2010.36
Online-Zugang:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1038/cddis.2010.36
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/cddis201036
Volltext
Verfasserangaben:G.H. Wabnitz, C. Goursot, B. Jahraus, H. Kirchgessner, A. Hellwig, M. Klemke, M.H. Konstandin and Y. Samstag
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 19.09.2023
Beschreibung:Online Resource
ISSN:2041-4889
DOI:10.1038/cddis.2010.36

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