[Molecular mechanism of early-onset familial PD].

The cellular abnormalities in Parkinson's disease (PD) are probably induced by both genetic predisposition and environmental factors. Mitochondrial dysfunction has long been implicated in the pathogenesis of PD. The recent discovery of genes associated with the etiology of familial PD has emphasized the role of mitochondrial dysfunction in PD. Recently, PINK1 and Parkin, which are associated with the mitochondria, have also enhanced the understanding of mitochondrial integrity. However, the exact mechanism underlying the functional interplay between Parkin and PINK1 remains unknown. PINK1 is rapidly and constitutively degraded under steady state conditions in a mitochondrial membrane potential dependent manner. But a loss of mitochondrial potential stabilizes PINK1 accumulation. This phenomenon may be the first step of mitochondrial elimination (mitophagy) and useful for the mitochondrial stress biomarker. Furthermore, some pathogenic mutations of PINK1 are associated with mitochondrial respiratory deficit. These results suggest that accumulation of damaged mitochondria may be the cause of early-onset familial PD.