A novel role for cytochrome c: Efficient catalysis of S-nitrosothiol formation.
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.
Basu
Swati
S
Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA.
Keszler
Agnes
A
Azarova
Natalia A
NA
Nwanze
Nneka
N
Perlegas
Andreas
A
Shiva
Sruti
S
Broniowska
Katarzyna A
KA
Hogg
Neil
N
Kim-Shapiro
Daniel B
DB
D000818:Animals; D017209:Apoptosis; D002384:Catalysis; D002417:Cattle; D002457:Cell Extracts; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D006736:Horses; D066298:In Vitro Techniques; D008929:Mitochondria, Heart; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D015538:Nitrosation; D015398:Signal Transduction; D013367:Submitochondrial Particles; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*
D002457:Cell Extracts; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D045304:Cytochromes c; D042967:Electron Transport Complex I; D005978:Glutathione