Poly-ADP-ribose assisted protein localization resolves that DJ-1, but not LRRK2 or α-synuclein, is localized to the mitochondrial matrix

Several proteins linked to familial Parkinson disease have been associated with mitochondrial (dys-)function and have been described to reside within mitochondria. The putative mitochondrial and sub-mitochondrial localization of these proteins remains disputed, however, potentially due to conflicting results obtained by diverging technical approaches. Using the high-resolution poly-ADP-ribose assisted protein localization assay that also allows for detection of low level and even partial mitochondrial matrix localization, we demonstrate here that DJ-1, but not LRRK2 or alpha-synuclein, resides in the mitochondrial matrix. The localization of the proteins was not changed in cellular stress models of Parkinson disease and, in case of alpha-synuclein, not affected by pathological mutations. Our results verify the ability of DJ-1 to carry out its role also from within mitochondria and suggest that LRRK2 and alpha-synuclein may interact with and affect mitochondria from outside the mitochondrial matrix.