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FMN reduces Amyloid-β toxicity in yeast by regulating redox status and cellular metabolism

Author

Listed:
  • Xin Chen

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Boyang Ji

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Xinxin Hao

    (University of Gothenburg)

  • Xiaowei Li

    (Chalmers University of Technology)

  • Frederik Eisele

    (University of Gothenburg)

  • Thomas Nyström

    (University of Gothenburg)

  • Dina Petranovic

    (Chalmers University of Technology
    Chalmers University of Technology)

Abstract

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.

Suggested Citation

  • Xin Chen & Boyang Ji & Xinxin Hao & Xiaowei Li & Frederik Eisele & Thomas Nyström & Dina Petranovic, 2020. "FMN reduces Amyloid-β toxicity in yeast by regulating redox status and cellular metabolism," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14525-4
    DOI: 10.1038/s41467-020-14525-4
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    Cited by:

    1. Feiran Li & Yu Chen & Qi Qi & Yanyan Wang & Le Yuan & Mingtao Huang & Ibrahim E. Elsemman & Amir Feizi & Eduard J. Kerkhoven & Jens Nielsen, 2022. "Improving recombinant protein production by yeast through genome-scale modeling using proteome constraints," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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