S-nitrosylation of mitochondrial caspases

被引:306
作者
Mannick, JB
Schonhoff, C
Papeta, N
Ghafourifar, P
Szibor, M
Fang, KZ
Gaston, B
机构
[1] Univ Massachusetts, Sch Med, Dept Med, Shrewsbury, MA 01545 USA
[2] Beth Israel Hosp, Dept Med, Boston, MA 02115 USA
[3] Univ Virginia, Hlth Sci Ctr, Dept Pediat, Charlottesville, VA 22908 USA
关键词
nitric oxide; caspase-3; caspase-9; mitochondria; S-nitrosylation;
D O I
10.1083/jcb.200104008
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Caspase-3 is a cysteine protease located in both the cytoplasm and mitochondrial intermembrane space that is a central effector of many apoptotic pathways. In resting cells, a subset of caspase-3 zymogens is S-nitrosylated at the active site cysteine, inhibiting enzyme activity. During Fas-induced apoptosis, caspases are denitrosylated, allowing the catalytic site to function. In the current studies, we sought to identify the subpopulation of caspases that is regulated by S-nitrosylation. We report that the majority of mitochondrial, but not cytoplasmic, caspase-3 zymogens contain this inhibitory modification. In addition, the majority of mitochondrial caspase-9 is S-nitrosylated. These studies suggest that S-nitrosylation plays an important role in regulating mitochondrial caspase function and that the S-nitrosylation state of a given protein depends on its subcellular localization.
引用
收藏
页码:1111 / 1116
页数:6
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