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

作者：Wabnitz G H^*; Goursot C; Jahraus B; Kirchgessner H; Hellwig A; Klemke M; Konstandin M H; Samstag Y

来源：Cell Death & Disease, 2010, 1(7): e58.

DOI：10.1038/cddis.2010.36

• necrotic-like PCD
• T-cell immunity
• mitochondria
• microenvironment

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. Cell Death and Disease (2010) 1, e58; doi:10.1038/cddis.2010.36; published online 22 July 2010

• 出版日期2010-7