251. A novel role for cytochrome c: Efficient catalysis of S-nitrosothiol formation.
- Author
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Basu S, Keszler A, Azarova NA, Nwanze N, Perlegas A, Shiva S, Broniowska KA, Hogg N, and Kim-Shapiro DB
- Subjects
- Animals, Apoptosis, Catalysis, Cattle, Cell Extracts, Cytochromes c chemistry, Electron Transport Complex I metabolism, Glutathione analogs & derivatives, Glutathione chemistry, Horses, In Vitro Techniques, Mitochondria, Heart, Nitric Oxide chemistry, Signal Transduction, Submitochondrial Particles, Sulfhydryl Compounds chemistry, Cytochromes c metabolism, Glutathione metabolism, Nitric Oxide metabolism, Nitrosation, Sulfhydryl Compounds metabolism
- Abstract
Although S-nitrosothiols are regarded as important elements of many NO-dependent signal transduction pathways, the physiological mechanism of their formation remains elusive. Here, we demonstrate a novel mechanism by which cytochrome c may represent an efficient catalyst of S-nitrosation in vivo. In this mechanism, initial binding of glutathione to ferric cytochrome c is followed by reaction of NO with this complex, yielding ferrous cytochrome c and S-nitrosoglutathione (GSNO). We show that when submitochondrial particles or cell lysates are exposed to NO in the presence of cytochrome c, there is a robust formation of protein S-nitrosothiols. In the case of submitochondrial particles protein S-nitrosation is paralleled by an inhibition of mitochondrial complex I. These observations raise the possibility that cytochrome c is a mediator of S-nitrosation in biological systems, particularly during hypoxia, and that release of cytochrome c into the cytosol during apoptosis potentially releases a GSNO synthase activity that could modulate apoptotic signaling., (Copyright 2009 Elsevier Inc. All rights reserved.)
- Published
- 2010
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