This study explores how mutations in the DJ-1 gene, linked to Parkinson's disease (PD), interact with oxidative stress and antioxidant mechanisms. We examined whether DJ-1 is a substrate for sulfiredoxin (Srx), an antioxidant that repairs oxidative damage. By testing mutant flies lacking DJ-1β, jafrac1 (Prdx-2), or Srx under oxidative stress, we found that the absence of Srx and DJ-1β led to varied stress responses, suggesting that other pathways may help maintain antioxidant defenses. These findings underline the complexity of DJ-1, Srx, and oxidative stress interactions, offering new directions for PD treatments to reduce oxidative damage.