Parkinson’s disease is a prevalent and progressive neurodegenerative disorder characterized by motor deficits, loss of dopaminergic neurons in the substantia nigra pars compacta leading to dopamine depletion in the striatum. The mainstay of treatment is dopamine replacement therapy. We studied the effects of dopamine in PINK1 associated PD. Loss of PINK1 function causes mitochondrial dysfunction with calcium dysregulation and susceptibility to neuronal death. However the basis for dopaminergic neuronal vulnerability in sporadic and genetic forms of PD is not clear. We demonstrate that low concentrations of dopamine induce cell death in PINK1 deficient cells, but not WT cells, by mitochondrial depolarisation induced by mitochondrial permeability transition pore (mPTP) opening. Dopamine-induced mPTP opening was dependent on a combination of ROS production and calcium signalling. Dopamine induced cell death could be prevented by application of antioxidants, inhibition of ROS production and by respiratory chain substrates. Importantly, we also found that dopamine-induced calcium signal in astrocytes can be blocked by antioxidants. The mechanism of this calcium signal is initiated by metabolites of dopamine produced by monoamine oxidase, which generate hydrogen peroxide that lead to induction of lipid peroxidation. This stimulates the activation of phospholipase C, and subsequent release of calcium from the endoplasmic reticulum via the IP3-receptor mechanism. These findings demonstrate that reactive oxygen species can play a physiological role in healthy cells but can also induce pathology and cell death in cells with genetic forms of PD, thus helping us to better understanding the physiological role of dopamine and mechanisms of neurodegeneration.