Overexpression of Buffy enhances the loss of parkin and suppresses the loss of Pink1 phenotypes in Drosophila

Abstract

Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson's disease (PD). Attributed to the failure of neurons to clear dysfunctional mitochondria, loss of gene expression leads to loss of nigrostriatal neurons. The Pink1/parkin pathway plays a role in the quality control mechanism aimed at eliminating defective mitochondria, and the failure of this mechanism results in a reduced lifespan and impaired locomotor ability, among other phenotypes. Inhibition of parkin or Pink1 through the induction of stable RNAi transgene in the Ddc-Gal4-expressing neurons results in such phenotypes to model PD. To further evaluate the effects of the overexpression of the Bcl-2 homologue Buffy, we analysed lifespan and climbing ability in both parkin-RNAi- and Pink1-RNAi-expressing flies. In addition, the effect of Buffy overexpression upon parkin-induced developmental eye defects was examined through GMR-Gal4-dependent expression. Curiously, Buffy overexpression produced very different effects: the parkin-induced phenotypes were enhanced, whereas the Pink1-enhanced phenotypes were suppressed. Interestingly, the overexpression of Buffy along with the inhibition of parkin in the neuron-rich eye results in the suppression of the developmental eye defects.

Alteration of Drp1 Expression in Drosophila Models of Parkinson Disease

“…The collected ies were kept as cohorts of 10 ies or less upon fresh media and allowed to age for 3 to 4 days. The ies were prepared for scanning electron microscopy following the standard protocol [35]. Ommatidia and interommatidial bristle counts were performed on 10 or more ies of each genotype using National Institute of Health (NIH) ImageJ software.…”

“…Overexpression of Drp1 has toxic effects; although, its inhibition slightly improves the lifespan, the climbing ability over time is compromised. In an established park-RNAi model of PD [35], we directed and inhibited the expression of the Drp1 gene. The PD -like phenotypes of Ddc-Gal4 park RNAi were rescued by the expression of Drp1-RNAi transgenes.…”