FMN reduces Amyloid-β toxicity in yeast by regulating redox status and cellular metabolism
Journal article, 2020

Alzheimer's disease (AD) is defined by progressive neurodegeneration, with oligomerization and aggregation of amyloid-β peptides (Aβ) playing a pivotal role in its pathogenesis. In recent years, the yeast Saccharomyces cerevisiae has been successfully used to clarify the roles of different human proteins involved in neurodegeneration. Here, we report a genome-wide synthetic genetic interaction array to identify toxicity modifiers of Aβ42, using yeast as the model organism. We find that FMN1, the gene encoding riboflavin kinase, and its metabolic product flavin mononucleotide (FMN) reduce Aβ42 toxicity. Classic experimental analyses combined with RNAseq show the effects of FMN supplementation to include reducing misfolded protein load, altering cellular metabolism, increasing NADH/(NADH + NAD+) and NADPH/(NADPH + NADP+) ratios and increasing resistance to oxidative stress. Additionally, FMN supplementation modifies Htt103QP toxicity and α-synuclein toxicity in the humanized yeast. Our findings offer insights for reducing cytotoxicity of Aβ42, and potentially other misfolded proteins, via FMN-dependent cellular pathways.

Author

Xin Chen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Boyang Ji

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Xinxin Hao

University of Gothenburg

Xiaowei Li

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Frederik Eisele

University of Gothenburg

Thomas Nyström

University of Gothenburg

Dina Petranovic Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Nature Communications

2041-1723 (ISSN)

Vol. 11 1 867-

Subject Categories

Cell Biology

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1038/s41467-020-14525-4

PubMed

32054832

More information

Latest update

4/3/2020 1