title: A dual signalling pathway for the hypoxic expression of lipid genes, dependent on the glucose sensor Rag4, is revealed by the analysis of the KlMGA2 gene in Kluyveromyces lactis.
abstract: In the respiratory yeast Kluyveromyces lactis, little is known about the factors regulating the metabolic response to oxygen shortage. After searching for homologues of characterized Saccharomyces cerevisiae regulators of the hypoxic response, we identified a gene that we named KlMGA2, which is homologous to MGA2. The deletion of KlMGA2 strongly reduced both the fermentative and respiratory growth rate and altered fatty acid composition and the unsaturation index of membranes. The reciprocal heterologous expression of MGA2 and KlMGA2 in the corresponding deletion mutant strains suggested that Mga2 and KlMga2 are functional homologues. KlMGA2 transcription was induced by hypoxia and the glucose sensor Rag4 mediated the hypoxic induction of KlMGA2. Transcription of lipid biosynthetic genes KlOLE1, KlERG1, KlFAS1 and KlATF1 was induced by hypoxia and was dependent on KlMga2, except for KlOLE1. Rag4 was required for hypoxic induction of transcription for both KlMga2-dependent (KlERG1) and KlMga2-independent (KlOLE1) structural genes.
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Micolonghi
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ottaviano
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Di Silvio
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damato
authors.affiliation: Department of Environmental Biotechnology, Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Heipieper
authors.affiliation: Pasteur Institut Cenci-Bolognetti Foundation, Sapienza University of Rome, Italy.|Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Bianchi
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D005816:Genetic Complementation Test; D005947:Glucose / Q000378:metabolism*; D007716:Kluyveromyces / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000235:genetics; D010100:Oxygen / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; C542266:MGA2 protein, S cerevisiae; D008565:Membrane Proteins; C435343:RAG4 protein, Kluyveromyces; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005947:Glucose; D010100:Oxygen