The strongest evidence for a mechanistic link between PD and the dysregulation of transcriptional programs for nuclear-encoded mitochondrial genes stems from two lines of investigation: identification of the mechanisms underlying neuronal vulnerability with PARKIN loss-of-function [181,182,183,184,185] and the transcriptional profiling of dopaminergic neurons from postmortem tissue of patients with Lewy pathology [186]. Here, PRKN is linked to Parkinson disease.