Dr. Sabrina Büttner, Department of Molecular Biosciences, Stockholm University
Tuesday 28th March, 1.00 p.m., Stacey Lecture Theatre 1
Since its introduction as experimental system almost one century ago, the yeast S. cerevisiae has advanced to one of the main model organisms used for the multifaceted analysis of complex biological processes, including the elucidation of the molecular pathways and subroutines underlying human disease. Major pathways governing autophagy, oxidative stress response, cell death, and in particular ageing are conserved between yeast and human. Hence, the yeast model has successfully contributed to our understanding of physiological and pathophysiological ageing in the mammalian systems. We use humanized yeast models to further understand the molecular basis of Parkinson’s disease -associated cellular demise. Heterologous expression of α-synuclein, a protein associated with both sporadic and hereditary Parkinson’s disease, leads to the death of yeast cells in an age-dependent manner. Our data indicates that this is in part caused by general lysosomal dysfunction and a block in autophagy. Interestingly, we can link α-synuclein-induced impairment of autophagy and subsequent cellular demise to Ca2+ homeostasis and identify the evolutionary conserved Ca2+/calmodulin-dependent phosphatase calcineurin as essential mediator.