Martínez, A. 1, 2 , Clague, M. 1 , Urbé, S. 1 & Mayor, U. 2, 3
1 Institute of Translational Medicine University of Liverpool, Crown Street, Liverpool L69 3BX, UK
2 CIC Biogune, Bizkaia Teknologi Parkea, 48160 Derio
3 Ikerbasque - Basque Foundation for Science
Mitophagy is a type of autophagy by which defective mitochondria are selectively targeted and degraded. PINK1 and Parkin are master regulators of mitophagy and mutations in these genes cause Parkinson?s Disease (PD). How mitophagy is regulated and the mechanism by which its failure may cause PD is yet unclear. We are studying Parkin-dependent mitophagy using in vitro and in vivo models. Using RPE1 cells that stably overexpress YFP-Parkin we studied how mitophagy happens after CCCP treatment and checked for genes that modify this process. Our studies show that Parkin overexpression (in RPE1-YFP-Parkin cells) causes cell death when mitophagy is triggered with CCCP treatment, as compared to parental RPE1 cells. We also have overexpressed WT and Catalytic Inactive (CI) dParkin in Drosophila neurons. Reduced longevity and locomotor deficits appear when WT dParkin is overexpressed in Drosophila neurons. Further characterization of the effect and mechanisms regulated by Parkin could help to understand better what happens in patiens with PD.