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Published online 10 September 2001. doi:10.1083/jcb.200104008
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© The Rockefeller University Press, 0021-9525/2001/9/1111 $5.00
The Journal of Cell Biology, Volume 154, Number 6, September 17, 2001 1111-1116


Report

S-Nitrosylation of mitochondrial caspases



Joan B. Mannick1, Christopher Schonhoff1, Natalia Papeta2, Pedram Ghafourifar1, Marten Szibor1, Kezhong Fang3 and Benjamin Gaston3

1 Department of Medicine, University of Massachusetts Medical School, Shrewsbury, MA 01545
2 Department of Medicine, Beth Israel Hospital, Boston, MA 02115
3 Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, VA 22908

Address correspondence to Joan B. Mannick, Dept. of Medicine, University of Massachusetts Medical School, Rose Reed Gordon Bldg., 222 Maple Ave., Shrewsbury, MA 01545. Tel.: (508) 856-7511. Fax: (508) 856-7578. E-mail: joan.mannick{at}umassmed.edu

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.

Key Words: nitric oxide; caspase-3; caspase-9; mitochondria; S-nitrosylation


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