Soste, Martin Charmpi, Konstantina Lampert, Fabienne Gerez, Juan Atilio Oostrum, Marcvan Malinovska, Liliana Boersema, Paul Jonathan Prymaczok, Natalia Cecilia Riek, Roland Peter, Matthias Vanni, Stefano Beyer, Andreas Picotti, Paola 2019-09-25 Proteinaceous inclusions containing alpha-synuclein (α-Syn) have been implicated in neuronal toxicity in Parkinson’s disease, but the pathways that modulate toxicity remain enigmatic. Here, we used a targeted proteomic assay to simultaneously measure 269 pathway activation markers and proteins deregulated by α-Syn expression across a panel of 33 Saccharomyces cerevisiae strains that genetically modulate α-Syn toxicity. Applying multidimensional linear regression analysis to these data predicted Pah1, a phosphatase that catalyzes conversion of phosphatidic acid to diacylglycerol at the endoplasmic reticulum membrane, as an effector of rescue. Follow-up studies demonstrated that inhibition of Pah1 activity ameliorates the toxic effects of α-Syn, indicate that the diacylglycerol branch of lipid metabolism could enhance α-Syn neuronal cytotoxicity, and suggest a link between α-Syn toxicity and the biology of lipid droplets. application/pdf https://folia.unifr.ch/global/documents/308112 https://folia.unifr.ch/documents/308112/files/van_pbm.pdf https://folia.unifr.ch/documents/308112/files/van_pbm_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cels.2019.07.010 info:eu-repo/semantics/openAccess License undefined Cell Systems. - 2019, vol. 9, no. 3, p. 309-320.e8 info:eu-repo/classification/udc/57 Proteomics-based monitoring of pathway activity reveals that blocking diacylglycerol biosynthesis rescues from alpha-synuclein toxicity http://purl.org/coar/resource_type/c_6501