PubMed ID
11551979
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Date
9-12-2001
Document Type
Article
Subjects
Antigens, CD95; Caspase 3; Caspase 9; Caspases; Enzyme Precursors; Humans; Mitochondria; Nitric Oxide Synthase; Protein Sorting Signals; Protein Transport; Subcellular Fractions; Tumor Cells, Cultured
Disciplines
Cell Biology | Immunology and Infectious Disease
Abstract
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.
Rights and Permissions
Citation: J Cell Biol. 2001 Sep 17;154(6):1111-6. Epub 2001 Sep 10. Link to article on publisher's site