Properties of the Mitochondrial Permeability Transition in Drosophila S2R+ Cells

Abstract

The mitochondrial permeability transition, caused by factors such as reactive oxygen species or calcium overload, has been extensively studied in mammalian cells, but its presence remains in doubt in non-mammalian organisms. In Drosophila, prior studies have documented calcium-induced depolarization and release, but no obvious swelling. Here we show that Drosophila S2R+ cells do possess the machinery for permeability transition, but that its requirement for calcium overload is significantly higher than in mammalian systems. using a calcein-loading method, we show that Drosophila permeability transition can be triggered by calcium overload, using ionomycin, and by cysteine oxidation, using phenylarsine oxide. As in mammalian systems, pharmacological blockade of mitochondrial cyclophilin (cyclosporine A) or the ATP/ADP transporter (bongkrekic acid) inhibits the Drosophila permeability transition. Finally, we examine the pathways for calcium influx into S2R+ mitochondria to see if differences in these pathways between mammalian and Drosophila cells may partly explain the discrepancy in calcium requirement.