We have been using the budding yeast Saccharomyces cerevisiae to study the Parkinson's disease- related protein alpha synuclein (a-syn). We have discovered that yeast cells expressing wild-type a-syn (WT), or either of the two inherited mutants, A53T or A30P, exhibit several markers of apoptosis: externalization of phosphatidylserine, the accumulation of reactive oxygen species, and the release of cytochrome c from mitochondria into the cytosol. We also discovered that yeast cells expressing any of the three a-syns are very sensitive to killing by hydrogen peroxide, which is known inducer of apoptosis in yeast. This finding has been exploited to create a unique genetic screen. Genes from a high copy library that rescue hydrogen peroxide sensitivity may also suppress other traits of a-syn expression and provide insights into the mechanisms by which a-syn causes cell death. This method allows us to screen libraries of genes- genes from any organism-to discover genes that protect against a-syn toxicity. ? ?
| Liang, Jun; Clark-Dixon, Cheryl; Wang, Shaoxiao et al. (2008) Novel suppressors of alpha-synuclein toxicity identified using yeast. Hum Mol Genet 17:3784-95 |
| Flower, Todd R; Clark-Dixon, Cheryl; Metoyer, Cheynita et al. (2007) YGR198w (YPP1) targets A30P alpha-synuclein to the vacuole for degradation. J Cell Biol 177:1091-104 |
| Witt, Stephan N; Flower, Todd R (2006) alpha-Synuclein, oxidative stress and apoptosis from the perspective of a yeast model of Parkinson's disease. FEMS Yeast Res 6:1107-16 |
