title: Amyloid-β peptide-induced cytotoxicity and mitochondrial dysfunction in yeast.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by deposits of amyloid-β (Aβ) peptides. However, the underlying molecular mechanisms of neuron cell dysfunction and cell death in AD still remain poorly understood. Yeast Saccharomyces cerevisiae shares many conserved biological processes with all eukaryotic cells, including human neurons. Thanks to relatively simple and quick genetic and environmental manipulations, the large knowledge base and data collections, this organism has become a valuable tool to unravel fundamental intracellular mechanisms underlying neurodegeneration. In this study, we have used yeast as a model system to study the effects of intracellular Aβ peptides and we found that cells constitutively producing native Aβ directed to the secretory pathway exhibited a lower growth rate, lower biomass yield, lower respiratory rate, increased oxidative stress, hallmarks of mitochondrial dysfunction and ubiquitin-proteasome system dysfunction. These findings are relevant for better understanding the role of Aβ in cell stress and cell damage.
authors.affiliation: Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, SE-412 96 Göteborg, Sweden dina.petranovic@chalmers.se.
authors.forename: Dina
authors.initials: D
authors.lastname: Petranovic
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D059748:Proteolysis / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's disease; Amyloid-β; mitochondria; oxidative stress; ubiquitin-proteasome system; yeast