Novel roles for ion transporters in cell death pathways in budding yeast

Mitochondria are essential for most of the apoptotic processes in animals and in yeast. Both high pheromone and amiodarone were reported to trigger the sequential apoptotic changes in mitochondria. Here we report the involvement of ion transporters in uncoupling calcium bursts from yeast cell death in PCD pathways. First, members of the TRPML-like FLC family of calcium channels are required not only for pheromone-induced calcium influx, but also for pheromone-induced cell cycle arrest. Nevertheless, they are completely defective in conjugation, showing that calcium transporters can be required for pheromone sensing at least in rich medium. Second, mutants in ATP6 encoded subunit of F0/F1 H+-ATPase are defective in amiodarone induced mitochondrial calcium burst, but they are equally sensitive to amiodarone. The antiarrhythmic drug amiodarone has fungicidal activity against a broad range of fungi. In Saccharomyces cerevisiae, it elicits an immediate influx of Ca2+ followed by mitochondrial fragmentation and eventual cell death. Non-mitochondrial or non-calcium involving events following amiodarone exposure seem to be sufficient for cell death programme activation.