title: Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae.
abstract: Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants. While elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. Further our work suggests that NuA4 regulates acetyl-CoA levels through the Acetyl-CoA carboxylase Acc1. Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules.
authors.affiliation: Ottawa Institute of Systems Biology, uOttawa, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Meaghen
authors.identifier: 0000-0001-8469-0763
authors.initials: M
authors.lastname: Rollins
authors.affiliation: Ottawa Institute of Systems Biology, uOttawa, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Huard
authors.affiliation: Department of Cellular and Molecular Medicine, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Morettin
authors.affiliation: Ottawa Institute of Systems Biology, uOttawa, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Jennifer
authors.identifier: 0000-0002-2745-2117
authors.initials: J
authors.lastname: Takuski
authors.affiliation: Ottawa Institute of Systems Biology, uOttawa, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Trang Thuy
authors.identifier: 0000-0001-9739-1009
authors.initials: TT
authors.lastname: Pham
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Morgan D
authors.initials: MD
authors.lastname: Fullerton
authors.affiliation: Department of Cellular and Molecular Medicine, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Côté
authors.affiliation: Ottawa Institute of Systems Biology, uOttawa, Ottawa, Ontario, Canada.|Department of Biochemistry, Microbiology and Immunology, uOttawa, Ottawa, Ontario, Canada.
authors.forename: Kristin
authors.identifier: 0000-0002-7312-195X
authors.initials: K
authors.lastname: Baetz
mesh_terms: D000105:Acetyl Coenzyme A / Q000235:genetics*; D000123:Acetyltransferases / Q000235:genetics*; D005947:Glucose / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D050505:Mutant Proteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C504740:NuA4 protein, S cerevisiae; D005947:Glucose