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

Bianca M. Esch, Sergej Limar, André Bogdanowski, Christos Gournas, Tushar More, Celine Sundag, Stefan Walter, Jürgen J. Heinisch, Christer S. Ejsing, Bruno André, Florian Fröhlich*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Artikelnummere1008745
TidsskriftPLOS Genetics
Vol/bind16
Udgave nummer8
ISSN1553-7390
DOI
StatusUdgivet - 26. aug. 2020

Fingeraftryk Dyk ned i forskningsemnerne om 'Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae'. Sammen danner de et unikt fingeraftryk.

  • Citationsformater

    Esch, B. M., Limar, S., Bogdanowski, A., Gournas, C., More, T., Sundag, C., Walter, S., Heinisch, J. J., Ejsing, C. S., André, B., & Fröhlich, F. (2020). Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae. PLOS Genetics, 16(8), [e1008745]. https://doi.org/10.1371/JOURNAL.PGEN.1008745