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A Yeast Global Genetic Screen Reveals that Metformin Induces an Iron Deficiency-Like State

B. Stynen, D. Abd-Rabbo, J. Kowarzyk, L. Miller-Fleming, M. Ralser, S.W. Michnick
doi: https://doi.org/10.1101/190389
B. Stynen
1Département de Biochimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, H3C 3J7, Canada.
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D. Abd-Rabbo
1Département de Biochimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, H3C 3J7, Canada.
5Centre Robert-Cedergren, Bio-Informatique et Génomique, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, H3C 3J7, Canada.
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J. Kowarzyk
1Département de Biochimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, H3C 3J7, Canada.
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L. Miller-Fleming
2Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
3Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
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M. Ralser
2Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
3Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom
4The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London, 1 Midland Rd, NW11AT, United Kingdom
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S.W. Michnick
1Département de Biochimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, H3C 3J7, Canada.
5Centre Robert-Cedergren, Bio-Informatique et Génomique, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, H3C 3J7, Canada.
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  • For correspondence: stephen.michnick@umontreal.ca
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Abstract

We report here a simple and global strategy to map out gene functions and target pathways of drugs, toxins or other small molecules based on “homomer dynamics” Protein-fragment Complementation Assays (hdPCA). hdPCA measures changes in self-association (homomerization) of over 3,500 yeast proteins in yeast grown under different conditions. hdPCA complements genetic interaction measurements while eliminating confounding effects of gene ablation. We demonstrate that hdPCA accurately predicts the effects of two longevity and health-span-affecting drugs, immunosuppressant rapamycin and type II diabetes drug metformin, on cellular pathways. We also discovered an unsuspected global cellular response to metformin that resembles iron deficiency. This discovery opens a new avenue to investigate molecular mechanisms for the prevention or treatments of diabetes, cancers and other chronic diseases of aging.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 18, 2017.
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A Yeast Global Genetic Screen Reveals that Metformin Induces an Iron Deficiency-Like State
B. Stynen, D. Abd-Rabbo, J. Kowarzyk, L. Miller-Fleming, M. Ralser, S.W. Michnick
bioRxiv 190389; doi: https://doi.org/10.1101/190389
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A Yeast Global Genetic Screen Reveals that Metformin Induces an Iron Deficiency-Like State
B. Stynen, D. Abd-Rabbo, J. Kowarzyk, L. Miller-Fleming, M. Ralser, S.W. Michnick
bioRxiv 190389; doi: https://doi.org/10.1101/190389

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