Although the exact mechanism(s) of the degeneration of dopaminergic neurons in Parkinson's disease (PD) is not well understood, mitochondrial dysfunction is proposed to play a central role. This proposal is strongly strengthened by the findings that compromised mitochondrial functions and/or exposure to mitochondrial toxins such as rotenone, paraquat, or MPTP causes degeneration of the midbrain dopaminergic system and manifest symptoms similar to Parkinson's disease in primates and rodents (Goldman, 2014). In fact, the specific dopaminergic toxin MPTP is one of the most commonly used models in the mechanistic studies of environmental factors associated with the etiology of PD, particularly due to the availability of direct and unequivocal clinical and biochemical evidence from human and primate subjects. Several decades of intense studies in many laboratories have led to the proposition of a general mechanism for the specific dopaminergic toxicity of MPTP (Przedborski and Jackson-Lewis, 1998). The salient features of this mechanism are (a) lipophilic pro-toxin, MPTP, freely crosses the blood-brain barrier and enters the brain; (b) in glial cells monoamine oxidase-B converts it to the toxic metabolite MPP+; (c) the polar MPP+ is extruded into the extracellular space through organic cation transporter-3; (d) presynaptic dopamine transporter (DAT) takes it up specifically into dopaminergic neurons; (e) in dopaminergic neurons, MPP+ accumulates in the synaptic vesicles and/or mitochondria; (f) mitochondrial MPP+ inhibits the mitochondrial complex-I of the electron transport chain, leading to cellular ATP depletion and excessive reactive oxygen species (ROS) production causing apoptotic cell death (Lotharius and O’Malley, 2000; Storch et al., 2004). Although this mechanism is generally well accepted, numerous recent studies seriously challenge the central dogma of this proposal that the specific dopaminergic toxicity of MPP+ is primarily due to the specific uptake into dopaminergic neurons through presynaptic DAT.