Metabolism of S-nitrosoglutathione in intact mitochondria

Citation
M. Steffen et al., Metabolism of S-nitrosoglutathione in intact mitochondria, BIOCHEM J, 356, 2001, pp. 395-402
Citations number
42
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL JOURNAL
ISSN journal
02646021 → ACNP
Volume
356
Year of publication
2001
Part
2
Pages
395 - 402
Database
ISI
SICI code
0264-6021(20010601)356:<395:MOSIIM>2.0.ZU;2-V
Abstract
S-nitrosation of protein thiol groups by nitric oxide (NO.) is a widely rec ognized protein modification. Only few intracellular S-nitrosated proteins have been identified and it has been reported that S-nitrosation/denitrosat ion can serve as a regulatory process in si,anal-transduction pathways. Giv en the potential physiological importance of S-nitrosothiols, and consideri ng that mitochondria are endowed with high levels of thiols and the biochem ical requisites for synthesizing NO., we examined the occurrence of S-nitro soglutathione (GSNO) in intact, coupled rat liver mitochondria. These organ elles contained 0.34 nmol of GSNO/mg of protein, detected by HPLC with UV-v isible and electrochemical detections. This concentration was dynamically m odulated by the availability of NO.; its decay was affected mainly by GSH a nd superoxide dismutase in a reaction that entailed the generation of GSSG. On the basis of the relatively long half-life of GSNO and the negligible r ecovery of NO. during its decay, roles for GSNO as a storage and transport molecule for NO. are discussed. Moreover, the formation of GSNO and its rea ction with GSH can be considered to be partly responsible for the catabolis m of NO. via a complex mechanism that might result in the formation of hydr oxylamine, nitrite or nitrous oxide depending upon the availability of oxyg en, superoxide dismutase and glutathione. Finally, the high concentrations of GSH in the cytosol and mitochondria might favour the formation of GSNO b y reacting with NO. 'in excess', thereby avoiding damaging side reactions ( such as peroxynitrite formation), and facilitate the inactivation of NO. by generating other nitrogen-related species without the chemical properties characteristic of NO..