Mutations in the nucleotide-binding domain of putative sterol importers Aus1 and Pdr11 selectively affect utilization of exogenous sterol species in yeast.


Journal

Yeast (Chichester, England)
ISSN: 1097-0061
Titre abrégé: Yeast
Pays: England
ID NLM: 8607637

Informations de publication

Date de publication:
01 2020
Historique:
received: 30 07 2019
revised: 08 12 2019
accepted: 10 12 2019
pubmed: 13 12 2019
medline: 20 3 2021
entrez: 13 12 2019
Statut: ppublish

Résumé

Sterol uptake in the yeast Saccharomyces cerevisiae is mediated by two plasma membrane ATP-binding cassette transporters, Aus1 and Pdr11. Their expression is regulated by oxygen and is triggered by anaerobic growth conditions. Under these conditions, internal ergosterol synthesis is arrested and utilization of exogenous sterol is vital for yeast cells. Here, we demonstrate that Aus1 is the major importer of non-yeast sterols, mammalian cholesterol, and plant sterols under anaerobic conditions. In contrast, uptake of yeast native sterol, ergosterol, is relatively low. This uptake could not be enhanced by overexpression of either of the transporters. Interestingly, overexpression of the minor importer Pdr11 resulted in a substantial import of non-yeast sterols. We show that mutation of the conserved residue in one of the ABC characteristic motifs-the H-loop in Aus1 and Pdr11-lowered their ATPase activity. The residual activity was sufficient to import exogenous sterols and to preserve cell viability. Importantly, the reduction of sterol import was dramatic for mammalian cholesterol and plant sterols, whereas import of yeast ergosterol was decreased only slightly indicating substrate selectivity of the sterol utilization process.

Identifiants

pubmed: 31830308
doi: 10.1002/yea.3456
doi:

Substances chimiques

ATP-Binding Cassette Transporters 0
AUS1 protein, S cerevisiae 0
PDR11 protein, S cerevisiae 0
Saccharomyces cerevisiae Proteins 0
Sterols 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5-14

Informations de copyright

© 2019 John Wiley & Sons, Ltd.

Références

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Auteurs

Marek Papay (M)

Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Centre of Biosciences of the Slovak Academy of Sciences, Bratislava, Slovakia.

Cornelia Klein (C)

Center for Medical Biochemistry, Max Perutz Labs Vienna, Campus Vienna Biocenter, Medical University of Vienna, Vienna, Austria.

Ivan Hapala (I)

Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Centre of Biosciences of the Slovak Academy of Sciences, Bratislava, Slovakia.

Livia Petriskova (L)

Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Centre of Biosciences of the Slovak Academy of Sciences, Bratislava, Slovakia.

Karl Kuchler (K)

Center for Medical Biochemistry, Max Perutz Labs Vienna, Campus Vienna Biocenter, Medical University of Vienna, Vienna, Austria.

Martin Valachovic (M)

Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Centre of Biosciences of the Slovak Academy of Sciences, Bratislava, Slovakia.

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