In the present study, our direct detection of sulfonated derivatives and subsequent aggregation of parkin in cell-based PD model, an increase in aggregated parkin in rats and primates exposed to mitochondrial complex I inhibitors and in PD brains, in conjunction with finding that parkin function is regulated by ROS, yields mechanistic insight into the chemical reactions of parkin under oxidative stress and their effect on UPS impairment. The gene discussed is PRKN; the disease is Parkinson disease.