title: Unsaturated fatty acids-dependent linkage between respiration and fermentation revealed by deletion of hypoxic regulatory KlMGA2 gene in the facultative anaerobe-respiratory yeast Kluyveromyces lactis.
abstract: In the yeast Kluyveromyces lactis, the inactivation of structural or regulatory glycolytic and fermentative genes generates obligate respiratory mutants which can be characterized by sensitivity to the mitochondrial drug antimycin A on glucose medium (Rag(-) phenotype). Rag(-) mutations can occasionally be generated by the inactivation of genes not evidently related to glycolysis or fermentation. One such gene is the hypoxic regulatory gene KlMGA2. In this work, we report a study of the many defects, in addition to the Rag(-) phenotype, generated by KlMGA2 deletion. We analyzed the fermentative and respiratory metabolism, mitochondrial functioning and morphology in the Klmga2Δ strain. We also examined alterations in the regulation of the expression of lipid biosynthetic genes, in particular fatty acids, ergosterol and cardiolipin, under hypoxic and cold stress and the phenotypic suppression by unsaturated fatty acids of the deleted strain. Results indicate that, despite the fact that the deleted mutant strain had a typical glycolytic/fermentative phenotype and KlMGA2 is a hypoxic regulatory gene, the deletion of this gene generated defects linked to mitochondrial functions suggesting new roles of this protein in the general regulation and cellular fitness of K. lactis. Supplementation of unsaturated fatty acids suppressed or modified these defects suggesting that KlMga2 modulates membrane functioning or membrane-associated functions, both cytoplasmic and mitochondrial.
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: Arianna
authors.initials: A
authors.lastname: Montanari
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: De Angelis
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Santomartino
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Visca
authors.affiliation: Department of Biotechnology and Biosciences, Bicocca University of Milan, p.zza Della Scienza 2, 20126 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Brambilla
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy Pasteur Institut Cenci-Bolognetti Foundation, p.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rinaldi
authors.affiliation: Departement of Environmental Biology, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bello
authors.affiliation: Departement of Environmental Biology, Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Reverberi
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, p.le Aldo Moro 5, 00185 Rome, Italy michele.bianchi@uniroma1.it.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Bianchi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002308:Cardiolipins / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D058639:Cold-Shock Response / Q000502:physiology; D004875:Ergosterol / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005285:Fermentation / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D007716:Kluyveromyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D001426:Bacterial Proteins; D002308:Cardiolipins; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D014157:Transcription Factors; D000968:Antimycin A; D005947:Glucose; D004875:Ergosterol
keywords: lipid; membranes; metabolism; mitochondria; transcription regulation