tailieunhanh - Báo cáo khoa học: Cysteine residues exposed on protein surfaces are the dominant intramitochondrial thiol and may protect against oxidative damage

Cysteine plays a number of important roles in protecting the cell from oxidative damage through its thiol functional group. These defensive func-tions are generally considered to be carried out by the low molecular weight thiol glutathione and by cysteine residues in the active sites of pro-teins such as thioredoxin and peroxiredoxin. | ỊFEBS Journal Cysteine residues exposed on protein surfaces are the dominant intramitochondrial thiol and may protect against oxidative damage Raquel Requejo Thomas R. Hurd Nikola J. Costa and Michael P. Murphy MRC MitochondrialBiology Unit Wellcome Trust MRC Building Cambridge UK Keywords cysteine glutathione mitochondria peroxynitrite protein thiol Correspondence M. P. Murphy MRC MitochondrialBiology Unit Wellcome Trust MRC Building Hills Road Cambridge CB2 0XY UK Fax 44 0 1223 252905 Tel 44 0 1223 252900 E-mail mpm@ Re-use of this article is permitted in accordance with the Terms and Conditions set out at http . com authorresources Received 17 November 2009 revised 1 January 2010 accepted 8 January 2010 doi 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 mM 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