title: Coordinate Regulation of Yeast Sterol Regulatory Element-binding Protein (SREBP) and Mga2 Transcription Factors.
abstract: The Mga2 and Sre1 transcription factors regulate oxygen-responsive lipid homeostasis in the fission yeastSchizosaccharomyces pombein a manner analogous to the mammalian sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 transcription factors. Mga2 and SREBP-1 regulate triacylglycerol and glycerophospholipid synthesis, whereas Sre1 and SREBP-2 regulate sterol synthesis. In mammals, a shared activation mechanism allows for coordinate regulation of SREBP-1 and SREBP-2. In contrast, distinct pathways activate fission yeast Mga2 and Sre1. Therefore, it is unclear whether and how these two related pathways are coordinated to maintain lipid balance in fission yeast. Previously, we showed that Sre1 cleavage is defective in the absence ofmga2Here, we report that this defect is due to deficient unsaturated fatty acid synthesis, resulting in aberrant membrane transport. This defect is recapitulated by treatment with the fatty acid synthase inhibitor cerulenin and is rescued by addition of exogenous unsaturated fatty acids. Furthermore, sterol synthesis inhibition blocks Mga2 pathway activation. Together, these data demonstrate that Sre1 and Mga2 are each regulated by the lipid product of the other transcription factor pathway, providing a source of coordination for these two branches of lipid synthesis.
authors.affiliation: From the Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Risa
authors.identifier: 0000-0001-6851-2932
authors.initials: R
authors.lastname: Burr
authors.affiliation: From the Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Emerson V
authors.initials: EV
authors.lastname: Stewart
authors.affiliation: From the Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 peter.espenshade@jhmi.edu.
authors.forename: Peter J
authors.identifier: 0000-0002-6433-0178
authors.initials: PJ
authors.lastname: Espenshade
mesh_terms: D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000172:deficiency; D015966:Gene Expression Regulation, Fungal; D050356:Lipid Metabolism; D012568:Schizosaccharomyces / Q000737:chemistry*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; C000620137:Mga2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D051779:Sterol Regulatory Element Binding Proteins; D013261:Sterols; D014157:Transcription Factors
keywords: SREBP; fatty acid metabolism; hypoxia; lipid metabolism; membrane transport; mga2; sre1; transcription regulation; yeast