The Trypanosoma cruzi Enzyme TcGPXI Is a Glycosomal Peroxidase and Can Be Linked to Trypanothione Reduction by Glutathione or Tryparedoxin

摘要: Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, parasite-specific thiol, by glutathione. Here we show that TcGPXI also be trypanothione an alternative pathway involving thioredoxin-like protein tryparedoxin. The presence this new was first detected using dialyzed soluble fractions parasite extract. Tryparedoxin identified as intermediate molecule following purification, sequence analysis, antibody studies, reconstitution vitro. system readily saturated rate-limiting step being interaction with Both tryparedoxin operate ping-pong mechanism. Overexpression transfected parasites confers increased resistance exogenous hydroperoxides. contains carboxyl-terminal tripeptide (ARI) could act targeting signal for glycosome, kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, biochemical fractionation, have demonstrated localized both glycosome cytosol. ability use electron donors may reflect their availability at corresponding subcellular sites.