Metabolism of S-nitrosoglutathione in intact mitochondria

M. Steffen, T. M. Sarkela, A. A. Gybina, T. W. Steele, N. J. Trasseth, D. Kuehl, Cecilia R Giulivi

Research output: Contribution to journalArticle

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Abstract

S-nitrosation of protein thiol groups by nitric oxide (NO·) is a widely recognized protein modification. Only few intracellular S-nitrosated proteins have been identified and it has been reported that S-nitrosation/denitrosation can serve as a regulatory process in signal-transduction pathways. Given the potential physiological importance of S-nitrosothiols, and considering that mitochondria are endowed with high levels of thiols and the biochemical requisites for synthesizing NO·, we examined the occurrence of S-nitrosoglutathione (GSNO) in intact, coupled rat liver mitochondria. These organelles contained 0.34 nmol of GSNO/mg of protein, detected by HPLC with UV-visible and electrochemical detections. This concentration was dynamically modulated by the availability of NO·; its decay was affected mainly by GSH and 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 recovery 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 reaction with GSH can be considered to be partly responsible for the catabolism of NO· via a complex mechanism that might result in the formation of hydroxylamine, nitrite or nitrous oxide depending upon the availability of oxygen, superoxide dismutase and glutathione. Finally, the high concentrations of GSH in the cytosol and mitochondria might favour the formation of GSNO by 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·.

Original languageEnglish (US)
Pages (from-to)395-402
Number of pages8
JournalBiochemical Journal
Volume356
Issue number2
DOIs
StatePublished - Jun 1 2001
Externally publishedYes

Fingerprint

S-Nitrosoglutathione
Mitochondria
Metabolism
Nitric Oxide
Nitrosation
Protein S
Sulfhydryl Compounds
Superoxide Dismutase
S-Nitrosothiols
Availability
Signal transduction
Hydroxylamine
Proteins
Peroxynitrous Acid
Glutathione Disulfide
Liver Mitochondrion
Nitrous Oxide
Nitrites
Organelles
Liver

Keywords

  • Nitric oxide
  • Nitric oxide synthase
  • Nitrosothiols
  • Oxygen radicals
  • Transnitrosation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Steffen, M., Sarkela, T. M., Gybina, A. A., Steele, T. W., Trasseth, N. J., Kuehl, D., & Giulivi, C. R. (2001). Metabolism of S-nitrosoglutathione in intact mitochondria. Biochemical Journal, 356(2), 395-402. https://doi.org/10.1042/0264-6021:3560395

Metabolism of S-nitrosoglutathione in intact mitochondria. / Steffen, M.; Sarkela, T. M.; Gybina, A. A.; Steele, T. W.; Trasseth, N. J.; Kuehl, D.; Giulivi, Cecilia R.

In: Biochemical Journal, Vol. 356, No. 2, 01.06.2001, p. 395-402.

Research output: Contribution to journalArticle

Steffen, M, Sarkela, TM, Gybina, AA, Steele, TW, Trasseth, NJ, Kuehl, D & Giulivi, CR 2001, 'Metabolism of S-nitrosoglutathione in intact mitochondria', Biochemical Journal, vol. 356, no. 2, pp. 395-402. https://doi.org/10.1042/0264-6021:3560395
Steffen M, Sarkela TM, Gybina AA, Steele TW, Trasseth NJ, Kuehl D et al. Metabolism of S-nitrosoglutathione in intact mitochondria. Biochemical Journal. 2001 Jun 1;356(2):395-402. https://doi.org/10.1042/0264-6021:3560395
Steffen, M. ; Sarkela, T. M. ; Gybina, A. A. ; Steele, T. W. ; Trasseth, N. J. ; Kuehl, D. ; Giulivi, Cecilia R. / Metabolism of S-nitrosoglutathione in intact mitochondria. In: Biochemical Journal. 2001 ; Vol. 356, No. 2. pp. 395-402.
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