PT  - JOURNAL ARTICLE
AU  - B. Stynen
AU  - D. Abd-Rabbo
AU  - J. Kowarzyk
AU  - L. Miller-Fleming
AU  - M. Ralser
AU  - S.W. Michnick
TI  - A Yeast Global Genetic Screen Reveals that Metformin Induces an Iron Deficiency-Like State
AID  - 10.1101/190389
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 190389
4099  - http://biorxiv.org/content/early/2017/09/18/190389.short
4100  - http://biorxiv.org/content/early/2017/09/18/190389.full
AB  - 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.