Cited by 231Redox biology and oxidative stressSulfur Compounds in BiologyAntioxidant Activity and Oxidative Stress

Cysteine residues exposed on protein surfaces are the dominant intramitochondrial thiol and may protect against oxidative damage

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Requejo, Raquel, Hurd, Thomas R., Costa, Nikola J., Murphy, Michael P.·2010·The FEBS Journal

Abstract

Cysteine plays a number of important roles in protecting the cell from oxidative damage through its thiol functional group. These defensive functions are generally considered to be carried out by the low molecular weight thiol glutathione and by cysteine residues in the active sites of proteins such as thioredoxin and peroxiredoxin. In addition, there are thiols exposed on protein surfaces that are not directly involved with protein function, although they can interact with the intracellular environment. In the present study, in subcellular fractions prepared from rat liver or heart, we show that the quantitatively dominant free thiols are those of cysteine residues exposed on protein surfaces and not those carried by glutathione. Within the mitochondrial matrix, the concentration of exposed protein thiols is 60–90 m m, which is approximately 26‐fold higher than the glutathione concentration in that compartment. This suggests that exposed protein thiols are of greater importance than glutathione for nonenzyme catalysed reactions of thiols with reactive oxygen and nitrogen species and with electrophiles within the cell. One such antioxidant role for exposed protein thiols may be to prevent protein oxidative damage. In the present study, in mitochondrial membranes and in complex I, we show that exposed protein thiols protect against tyrosine nitration and protein dysfunction caused by peroxynitrite. Therefore, exposed protein thiols are the dominant free thiol within the cell and may play a critical role in intracellular antioxidant defences against oxidative damage.

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Crossref · 10.1111/j.1742-4658.2010.07576.x

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Authors
Requejo, R., Hurd, T. R., Costa, N. J., & Murphy, M. P.
Affiliations
MRC Mitochondrial Biology Unit (GB)
Venue
The FEBS Journal
Publisher
Wiley
Published
2010-02-24
Volume
277
Issue
6
Pages
1465-1480
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
OpenAlex
W1524076404
Cited by
231
References
52
Citations by year
2026: 7 · 2025: 7 · 2024: 14 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 11 · 2019: 13 · 2018: 20 · 2017: 11 · 2016: 14 · 2015: 18 · 2014: 24 · 2013: 16 · 2012: 14
FWCI
6.77
Type
journal article
Language
en
Open access
Locations
  • FEBS Journal (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Ministerio de Ciencia y Tecnología
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
cysteine residues, mitochondrial matrix, glutathione, oxidative damage, antioxidant defense, peroxynitrite, tyrosine nitration, protein oxidation, mitochondrial complex I, reactive oxygen species, reactive nitrogen species, electrophiles, rat liver, rat heart
MeSH terms
Animals, Cells, Cultured, Cysteine, Glutathione, Membrane Proteins, Mitochondria, Heart, Mitochondria, Liver, Sulfhydryl Compounds, Oxidative Stress, Rats

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