Exposure to environmental chemicals is a known risk factor for Parkinson's Disease (PD). Specifically, chemicals used in agriculture, (e.g. paraquat), are associated with PD. However, the exact relationship between exposure and disease is not known, and the underlying mechanism remains to be elucidated. Recent evidence suggests oxidative stress, but it is not known how these agents (e.g. paraquat) produce specific death of DA neurons as observed in PD. A potential mechanism may involve DA-derived endogenous neurotoxins, which would be found in DA regions of the brain. In this proposal, it is hypothesized that exposure of brain mitochondria to the herbicide paraquat results in accumulation of oxidized DA, specifically, DOPAL and/or the DA-quinone, yielding protein modification by these reactive compounds. Therefore, the studies described in this application seek to establish a mechanistic link between exposure to paraquat and aberrant levels of neurotoxic DA oxidation products proposed to participate in PD pathogenesis.