Abstract
Parkinson's disease (PD) is a neurodegenerative movement disorder in which mitochondrial dysfunction plays a prominent role. Several nuclear genes driving inherited forms of PD, such as PRKN, are linked to mitochondrial quality control mechanisms. The contribution of mitochondrial DNA (mtDNA) alterations to PD pathogenesis is still debated, but a link between mitochondrial defects, mtDNA damage and inflammatory signals has recently emerged.
Here, we characterized mitochondrial genomes in induced pluripotent stem cells (iPSC), iPSC-derived neurons, and blood-derived cells from PD patients, healthy heterozygous PRKN mutation carriers, and matched controls. Measurements of mtDNA structural integrity, mtDNA damage, as well as mtDNA sequencing, provided evidence for an altered mitochondrial quality control mechanism in PD-related mutation carriers. Deep mtDNA genotyping therefore allows to define a finer picture of the mtDNA alterations that may underlie mitochondrial defects in PD and paves the way for proposing biomarkers combining mitochondrial and inflammatory signatures.