This study investigates the role of parkin in mitochondrial function and oxidative stress in parkin-deficient mice. Parkin, an E3 ubiquitin ligase, is a key protein involved in familial Parkinson's disease (PD). The authors used proteomic analysis to compare the ventral midbrain of parkin−/− mice with wild-type mice, identifying 14 proteins involved in mitochondrial respiration or antioxidant activities that were decreased in abundance in parkin−/− mice. These proteins included subunits of complexes I and IV, peroxiredoxins, and lactoylglutathione lyase. Biochemical assays confirmed reduced respiratory capacity in striatal mitochondria from parkin−/− mice. Electron microscopy revealed no gross morphological abnormalities in striatal mitochondria. Additionally, parkin−/− mice showed delayed weight gain and increased serum antioxidant capacity and protein and lipid peroxidation. These findings suggest that parkin is essential for regulating mitochondrial function and protecting cells from oxidative stress, providing direct evidence of mitochondrial dysfunction and oxidative damage in a genetic mouse model of PD without nigral degeneration.This study investigates the role of parkin in mitochondrial function and oxidative stress in parkin-deficient mice. Parkin, an E3 ubiquitin ligase, is a key protein involved in familial Parkinson's disease (PD). The authors used proteomic analysis to compare the ventral midbrain of parkin−/− mice with wild-type mice, identifying 14 proteins involved in mitochondrial respiration or antioxidant activities that were decreased in abundance in parkin−/− mice. These proteins included subunits of complexes I and IV, peroxiredoxins, and lactoylglutathione lyase. Biochemical assays confirmed reduced respiratory capacity in striatal mitochondria from parkin−/− mice. Electron microscopy revealed no gross morphological abnormalities in striatal mitochondria. Additionally, parkin−/− mice showed delayed weight gain and increased serum antioxidant capacity and protein and lipid peroxidation. These findings suggest that parkin is essential for regulating mitochondrial function and protecting cells from oxidative stress, providing direct evidence of mitochondrial dysfunction and oxidative damage in a genetic mouse model of PD without nigral degeneration.