A Saccharomyces cerevisiae strain unable to store neutral lipids is tolerant to oxidative stress induced by α-synuclein

Parkinson disease is a neurodegenerative pathology that has been linked to several genetic mutations of the SNCA gene encoding the pro oxidant alpha synuclein protein The budding yeast Saccharomyces cerevisiae is a valuable model for studying the cellular and molecular mechanisms of alpha synuclein toxicity Indeed heterologous expression of alpha synuclein is toxic to wild-type yeast and exhibits the main features of damage caused to mammalian neurons including an increase in neutral lipid storage (triglycerides and steryl esters embedded into lipid droplets) To address the significance of this accumulation we forced alpha synuclein production in a strain unable to synthesize triglycerides and steryl esters Surprisingly the inability to store neutral lipids rendered the cells more tolerant to alpha synuclein Our results indicate that the level of alpha-synuclein toxicity is correlated with fatty acid synthase activity and intracellular redox status (C) 2010 Elsevier Inc All lights reserved