Mitochondrial translocation of cofilin is an early step in apoptosis induction

Speaker：林婷鈺

Commentator：劉校生老師

Time：03/17/2004 14:00~15:00

Place：601教室

Abstract:

Cofilin, an actin-binding protein, is a member of the cofilin/actin depolymerizing factor family, which modulates actin dynamics by increasing the rate of actin depolymerization and enhancing actin filament turnover (1). Mitochondria play a key role in regulation of apoptosis. Many apoptotic signals converge at mitochondria, and apoptogenic factors in mitochondria were leaked out into cytosol. Those events directly promote apoptosis (2). Although the role of mitochondria in controlling downstream apoptotic events is relatively well characterized, mechanisms by which the upstream apoptotic signaling utilized are still unclear. The authors used a proteomic analysis to find out that cofilin was translocated from cytosol into mitochondria when cells received apoptotic stimuli and induced mitochondrial-dependent cell death. Only dephosphorylated cofilin was translocated to mitochondria, and cofilin-mediated apoptosis was suppressed by cofilin siRNA, co-expression with Bcl-x_L, and caspase inhibitors. The N-terminal domain (cofilin^15-30) and the C-terminal region (cofilin^106-166) of cofilin are required for its mitochondrial localization, and a functional actin-binding domain of cofilin is crucial for its apoptosis-inducing activity (3). In addition to the previously known roles of cofilin in actin dynamics modulation, the authors’ findings suggest that cofilin is a potent inducer to initiate the caspase-dependent apoptosis.

References:

1.       Chen, H. et al. Regulating actin-filament dynamics in vivo. Trends Biochem. Sci. 25: 19-23, 2000.

2.       Newmeyer, D. D. et al. Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112: 481-490, 2003.

3.       Chua, B. T. et al. Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat. Cell Biol. 5: 1083-1089, 2003.