Mitochondrial translocation of oxidized cofilin induces caspase-independent necrotic-like programmed cell death of T cells

• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Verfasst von: Goursot, Catherine [VerfasserIn]
• Verfasst von: Jahraus, Beate [VerfasserIn]
• Verfasst von: Kirchgessner, Henning [VerfasserIn]
• Verfasst von: Hellwig, Andrea [VerfasserIn]
• Verfasst von: Klemke, Martin [VerfasserIn]
• Verfasst von: Konstandin, Mathias [VerfasserIn]
• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Titel: Mitochondrial translocation of oxidized cofilin induces caspase-independent necrotic-like programmed cell death of T cells
• Verf.angabe: G.H. Wabnitz, C. Goursot, B. Jahraus, H. Kirchgessner, A. Hellwig, M. Klemke, M.H. Konstandin and Y. Samstag
• E-Jahr: 2010
• Jahr: 22 July 2010
• Umfang: 12 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 19.09.2023
• Titel Quelle: Enthalten in: Cell death & disease
• Ort Quelle: London [u.a.] : Nature Publishing Group, 2010
• Jahr Quelle: 2010
• Band/Heft Quelle: 1(2010), 7, Artikel-ID e58, Seite 1-12
• ISSN Quelle: 2041-4889
• DOI: doi:10.1038/cddis.2010.36
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cancer microenvironment
• Sach-SW: Necroptosis
• Sach-SW: Protein translocation
• Sach-SW: T cells
• K10plus-PPN: 1859927769

Abstract

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.