Mitochondrial dysfunction and Parkinson’s disease genes: insights from Drosophila

Abstract

Parkinson’s disease (PD), one of the most common neurodegenerative disorders worldwide, currently lacks a cure. Although most PD cases occur sporadically, studies from rare genetic mutations give significant insights into addressing the pathological mechanism of not only familial PD, but also sporadic PD. Recent PD research focuses on generating genetic mutant animal models that recapitulate the features of human PD patients. Significant advances in PD research have resulted from studying Drosophila mutants of several identified PD-associated genes because they show strikingly visible phenotypes. In particular, previous studies with the Drosophila mutants parkin and PINK1, which are two common causative genes among PD familial forms, have suggested strongly that mitochondrial dysfunction is the prominent cause for the PD pathogenesis and that these two PD genes are in a common pathway, with Parkin downstream of PINK1. Recent genetic studies have revealed that the PINK1-Parkin pathway is involved in regulating the mitochondrial remodeling process. In addition, PINK1 was recently found to regulate the localization of Parkin through direct phosphorylation. Here, we briefly review these new and exciting findings in Drosophila PD models and discuss how using these models can further advance PD studies.