Mitochondrial 1-Cys-peroxiredoxin/thioredoxin system protects manganese-containing superoxide dismutase (Mn-SOD) against inactivation by peroxynitrite in Saccharomyces cerevisiae.
Peroxynitrite is a reactive nitrogen species that can mediate protein tyrosine nitration, inactivating many proteins. We show that yeast mitochondrial peroxiredoxin (Prx1p), which belongs to the group 1-Cys-Prx, has thioredoxin-dependent peroxynitrite reductase activity. This activity was characterised in vitro with the recombinant mitochondrial Prx1p, the thioredoxin reductase Trr2p and the thioredoxin Trx3p, using a generator of peroxynitrite (SIN-1). Purified mitochondria from wild-type and null Prx1p or Trx3p yeast strains, exposed to SIN-1, showed a differential inactivation of manganese-containing superoxide dismutase activity. The above yeast strains were exposed to SIN-1 and examined under confocal microscopy. Prx1p or Trx3p-null cells showed a greater accumulation of peroxynitrite than wild-type ones. Our results indicate that this 1-Cys-Prx is a peroxynitrite reductase activity that uses reducing equivalents from NADPH through the mitochondrial thioredoxin system. Therefore, mitochondrial 1-Cys-peroxiredoxin/thioredoxin system constitutes an essential antioxidant defence against oxidative and nitrosative stress in yeast mitochondria.
Pedrajas
José R
JR
Grupo de Señalización Molecular y Sistemas Antioxidantes en Plantas, Unidad Asociada al CSIC (EEZ), Area de Bioquímica y Biología Molecular, Departamento de Biología Experimental, Universidad de Jaén, E-23071 Jaén, Spain. pedrajas@ujaen.es
Carreras
Alfonso
A
Valderrama
Raquel
R
Barroso
Juan B
JB
D003545:Cysteine / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D008345:Manganese; D013879:Thioredoxins; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D003545:Cysteine