title: A novel role for cytochrome c: Efficient catalysis of S-nitrosothiol formation.
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.
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Basu
authors.forename: Agnes
authors.initials: A
authors.lastname: Keszler
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Azarova
authors.forename: Nneka
authors.initials: N
authors.lastname: Nwanze
authors.forename: Andreas
authors.initials: A
authors.lastname: Perlegas
authors.forename: Sruti
authors.initials: S
authors.lastname: Shiva
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Broniowska
authors.forename: Neil
authors.initials: N
authors.lastname: Hogg
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
mesh_terms: 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*
chemical_list: D002457:Cell Extracts; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D045304:Cytochromes c; D042967:Electron Transport Complex I; D005978:Glutathione