A novel role for cytochrome c: Efficient catalysis of S-nitrosothiol formation. Free Radic Biol Med 2010 Jan 15;48(2):255-63
Date
11/03/2009Pubmed ID
19879353Pubmed Central ID
PMC2818408DOI
10.1016/j.freeradbiomed.2009.10.049Scopus ID
2-s2.0-72649104434 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
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.
Author List
Basu S, Keszler A, Azarova NA, Nwanze N, Perlegas A, Shiva S, Broniowska KA, Hogg N, Kim-Shapiro DBAuthors
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinAgnes Keszler PhD Research Scientist I in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Catalysis
Cattle
Cell Extracts
Cytochromes c
Electron Transport Complex I
Glutathione
Horses
In Vitro Techniques
Mitochondria, Heart
Nitric Oxide
Nitrosation
Signal Transduction
Submitochondrial Particles
Sulfhydryl Compounds