Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae

English version

Autoři: Bianca M. Esch ^aff001; Sergej Limar ^aff001; André Bogdanowski ^aff002; Christos Gournas ^aff004; Tushar More ^aff005; Celine Sundag ^aff001; Stefan Walter ^aff006; Jürgen J. Heinisch ^aff007; Christer S. Ejsing ^aff005; Bruno André ^aff004; Florian Fröhlich ^aff001
Působiště autorů: Department of Biology/Chemistry, Molecular Membrane Biology Group, University of Osnabrück, Osnabrück, Germany ^aff001; Department of Biology/Chemistry, Ecology Group, University of Osnabrück, Osnabrück, Germany ^aff002; UFZ–Helmholtz Centre for Environmental Research Ltd, Department for Ecological Modelling, Leipzig, Germany ^aff003; Molecular Physiology of the Cell, Université Libre de Bruxelles (ULB), Institut de Biologie et de Médecine Moléculaires, Gosselies, Belgium ^aff004; Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark ^aff005; Center of Cellular Nanoanalytics Osnabrück, Osnabrück, Germany ^aff006; Department of Biology/Chemistry, Division of Genetics, University of Osnabrück, Osnabrück, Germany ^aff007; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany ^aff008
Vyšlo v časopise: Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae. PLoS Genet 16(8): e1008745. doi:10.1371/journal.pgen.1008745
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008745

Souhrn

Sphingolipids are abundant and essential molecules in eukaryotes that have crucial functions as signaling molecules and as membrane components. Sphingolipid biosynthesis starts in the endoplasmic reticulum with the condensation of serine and palmitoyl-CoA. Sphingolipid biosynthesis is highly regulated to maintain sphingolipid homeostasis. Even though, serine is an essential component of the sphingolipid biosynthesis pathway, its role in maintaining sphingolipid homeostasis has not been precisely studied. Here we show that serine uptake is an important factor for the regulation of sphingolipid biosynthesis in Saccharomyces cerevisiae. Using genetic experiments, we find the broad-specificity amino acid permease Gnp1 to be important for serine uptake. We confirm these results with serine uptake assays in gnp1Δ cells. We further show that uptake of exogenous serine by Gnp1 is important to maintain cellular serine levels and observe a specific connection between serine uptake and the first step of sphingolipid biosynthesis. Using mass spectrometry-based flux analysis, we further observed imported serine as the main source for de novo sphingolipid biosynthesis. Our results demonstrate that yeast cells preferentially use the uptake of exogenous serine to regulate sphingolipid biosynthesis. Our study can also be a starting point to analyze the role of serine uptake in mammalian sphingolipid metabolism.

Klíčová slova:

Amino acid analysis – Biosynthesis – Cell membranes – Homeostasis – Saccharomyces cerevisiae – Serine – Sphingolipids – Yeast

Zdroje

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