title: Yeast Saccharomyces cerevisiae adiponectin receptor homolog Izh2 is involved in the regulation of zinc, phospholipid and pH homeostasis.
abstract: The functional link between zinc homeostasis and membrane-related processes, including lipid metabolism regulation, extends from yeast to humans, and has a likely role in the pathogenesis of diabetes. The yeast Izh2 protein has been previously implicated in zinc ion homeostasis and in the regulation of lipid and phosphate metabolism, but its precise molecular function is not known. We performed a chemogenomics experiment to determine the genes conferring resistance or sensitivity to different environmental zinc concentrations. We then determined at normal, depleted and excess zinc concentrations, the genetic interactions of IZH2 at the genome-wide level and measured changes in the transcriptome caused by deletion of IZH2. We found evidence for an important cellular function of the Rim101 pathway in zinc homeostasis in neutral or acidic environments, and observed that phosphatidylinositol is a source of inositol when zinc availability is limited. Comparison of our experimental profiles with published gene expression and genetic interaction profiles revealed pleiotropic functions for Izh2. We propose that Izh2 acts as an integrator of intra- and extracellular signals in providing adequate cellular responses to maintain homeostasis under different external conditions, including - but not limited to - alterations in zinc concentrations.
authors.affiliation: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia. uros.petrovic@ijs.si.
authors.forename: Mojca
authors.initials: M
authors.lastname: Mattiazzi Ušaj
authors.forename: Metod
authors.initials: M
authors.lastname: Prelec
authors.forename: Mojca
authors.initials: M
authors.lastname: Brložnik
authors.forename: Cecilia
authors.initials: C
authors.lastname: Primo
authors.forename: Tomaž
authors.initials: T
authors.lastname: Curk
authors.forename: Janez
authors.initials: J
authors.lastname: Ščančar
authors.forename: Lynne
authors.initials: L
authors.lastname: Yenush
authors.forename: Uroš
authors.initials: U
authors.lastname: Petrovič
mesh_terms: D000136:Acid-Base Equilibrium; D027682:Cation Transport Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D007296:Myo-Inositol-1-Phosphate Synthase / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C497767:IZH2 protein, S cerevisiae; D008565:Membrane Proteins; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; C098750:ZRT1 protein, S cerevisiae; C519641:INO1 protein, S cerevisiae; D007296:Myo-Inositol-1-Phosphate Synthase; D015032:Zinc