title: Identification of Yeast Mutants Exhibiting Altered Sensitivity to Valinomycin and Nigericin Demonstrate Pleiotropic Effects of Ionophores on Cellular Processes.
abstract: Ionophores such as valinomycin and nigericin are potent tools for studying the impact of ion perturbance on cellular functions. To obtain a broader picture about molecular components involved in mediating the effects of these drugs on yeast cells under respiratory growth conditions, we performed a screening of the haploid deletion mutant library covering the Saccharomyces cerevisiae nonessential genes. We identified nearly 130 genes whose absence leads either to resistance or to hypersensitivity to valinomycin and/or nigericin. The processes affected by their protein products range from mitochondrial functions through ribosome biogenesis and telomere maintenance to vacuolar biogenesis and stress response. Comparison of the results with independent screenings performed by our and other laboratories demonstrates that although mitochondria might represent the main target for both ionophores, cellular response to the drugs is very complex and involves an intricate network of proteins connecting mitochondria, vacuoles, and other membrane compartments.
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Michaela
authors.initials: M
authors.lastname: Jakubkova
authors.affiliation: Department of Genetics, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Vladimira
authors.initials: V
authors.lastname: Dzugasova
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Dominika
authors.initials: D
authors.lastname: Truban
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.|Department of Genetics, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Lenka
authors.initials: L
authors.lastname: Abelovska
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bhatia-Kissova
authors.affiliation: Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Department of Biochemistry of Biomembranes, Moyzesova 61, 900 28 Ivanka pri Dunaji, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Valachovic
authors.affiliation: Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Department of Biochemistry of Biomembranes, Moyzesova 61, 900 28 Ivanka pri Dunaji, Slovakia.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Klobucnikova
authors.affiliation: Department of Genetics, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Zeiselova
authors.affiliation: Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Department of Biochemistry of Biomembranes, Moyzesova 61, 900 28 Ivanka pri Dunaji, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Griac
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Nosek
authors.affiliation: Department of Genetics, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
authors.forename: Lubomir
authors.identifier: http://orcid.org/0000-0003-4886-1910
authors.initials: L
authors.lastname: Tomaska
mesh_terms: D063990:Gene Ontology; D006863:Hydrogen-Ion Concentration; D007476:Ionophores / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D009550:Nigericin / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014617:Vacuoles / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology*
chemical_list: D007476:Ionophores; D029701:Saccharomyces cerevisiae Proteins; D014634:Valinomycin; D009550:Nigericin