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

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 regulat...

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Bibliographic Details
Published in:PLoS genetics 2020-08, Vol.16 (8), p.e1008745-e1008745
Main Authors: Esch, Bianca M, Limar, Sergej, Bogdanowski, André, Gournas, Christos, More, Tushar, Sundag, Celine, Walter, Stefan, Heinisch, Jürgen J, Ejsing, Christer S, André, Bruno, Fröhlich, Florian, Copenhaver, Gregory P, Dudley, Aimee M
Format: Article
Language:English
Subjects:
Amino acids
Biochemistry
Biology and Life Sciences
Biosynthesis
Chemistry
Endoplasmic reticulum
Enzymes
Genes
Genetic aspects
Homeostasis
Kinases
Laboratories
Lipid metabolism
Mass spectroscopy
Metabolism
Molecular biology
Permease
Physical Sciences
Physiological aspects
Physiology
Plasma
Proteins
Research and Analysis Methods
Saccharomyces cerevisiae
Serine
Sphingolipids
Sterols
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Summary: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 gnp1[DELTA] 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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1008745