Peroxiredoxin 6 Modulates Mitochondrial Function and Mitophagy in PINK1-Deficient Cells Under Oxidative Stress

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Mitochondrial dysfunction and impaired mitophagy are hallmark features of Parkinson’s disease (PD), especially in patients with mutations in the PINK1 gene. Peroxiredoxin 6 (Prx6) is a bifunctional antioxidant enzyme known for its protective roles under oxidative stress, but its effects on mitochondrial dynamics and mitophagy remain poorly understood. In this study, we investigated the impact of recombinant Prx6 on mitochondrial function, reactive oxygen species (ROS) production, and mitophagy in both wild-type (WT) and PINK1-mutant fibroblasts. We further assessed the expression of genes related to mitochondrial quality control in neuroblastoma SH-SY5Y cells.Prx6 treatment significantly reduced ROS production and preserved mitochondrial membrane potential under oxidative stress in both WT and PINK1-mutant fibroblasts. It enhanced basal mitophagy but dampened excessive mitophagic activation induced by H₂O₂. In SH-SY5Y cells, Prx6 upregulated multiple genes associated with mitochondrial fission/fusion (drp1, mfn2), mitophagy (parkin, pink1, optn), and cell survival (bcl2, nrf2).Our findings suggest that Prx6 promotes mitochondrial homeostasis and cellular resilience in PINK1-deficient conditions by modulating oxidative stress responses and mitophagy-related pathways. These results highlight the potential of Prx6 as a therapeutic candidate for PD and other neurodegenerative disorders involving mitochondrial dysfunction.

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