ATP‐binding cassette transporters and sterol
            <i>O</i>
            ‐acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification

Gulati, Sonia; Balderes, Dina; Kim, Christine; Guo, Zhongmin; Wilcox, Lisa J.; Area‐Gómez, Estela; Snider, Jamie; Wolinski, Heimo; Štagljar, Igor; Granato, Juliana T.; Ruggles, Kelly V.; DeGiorgis, Joseph A.; Kohlwein, Sepp D.; Schon, Eric A.; Sturley, Stephen L.

doi:10.1096/fj.14-264796

Cited by 23 publications

(22 citation statements)

References 55 publications

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“…Aus1 and Pdr11 form a complex in the plasma membrane and are together essential for sterol import [27,28,29]. DAN1 is another anaerobic gene whose expression is induced by Upc2 [27,30].…”

Section: Functions Of Ecm22 Upc2 Sut1 and Sut2 In Budding Yeastmentioning

confidence: 99%

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2

Joshua

Höfken

2017

IJMS

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Zinc cluster proteins are a large family of transcriptional regulators with a wide range of biological functions. The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae. These proteins also control adaptations to anaerobic growth, sterol biosynthesis as well as filamentation and mating. Orthologs of these zinc cluster proteins have been identified in several species of Candida. Upc2 plays a critical role in antifungal resistance in these important human fungal pathogens. Upc2 is therefore an interesting potential target for novel antifungals. In this review we discuss the functions, mode of actions and regulation of Ecm22, Upc2, Sut1 and Sut2 in budding yeast and Candida.

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“…Aus1 and Pdr11 form a complex in the plasma membrane and are together essential for sterol import [27,28,29]. DAN1 is another anaerobic gene whose expression is induced by Upc2 [27,30].…”

Section: Functions Of Ecm22 Upc2 Sut1 and Sut2 In Budding Yeastmentioning

confidence: 99%

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2

Joshua

Höfken

2017

IJMS

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“…The two enzymes are not influenced by the ergosterol concentration itself (no product inhibition). Moreover, studies have shown that an enhanced capacity to esterify sterols, in this case by the overexpression of ARE2 , which is localized directly at sterol‐rich microdomains (Gulati, Balderes, et al, ), can enrich the sterol content in yeast (Polakowski, Bastl, Stahl, & Lang, ). In the study of Rintala et al .…”

Section: Resultsmentioning

confidence: 99%

Sterol synthesis and cell size distribution under oscillatory growth conditions in Saccharomyces cerevisiae scale‐down cultivations

Marbà-Ardébol

Bockisch

Neubauer

et al. 2017

Yeast

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Physiological responses of yeast to oscillatory environments as they appear in the liquid phase in large-scale bioreactors have been the subject of past studies. So far, however, the impact on the sterol content and intracellular regulation remains to be investigated. Since oxygen is a cofactor in several reaction steps within sterol metabolism, changes in oxygen availability, as occurs in production-scale aerated bioreactors, might have an influence on the regulation and incorporation of free sterols into the cell lipid layer. Therefore, sterol and fatty acid synthesis in two- and three-compartment scale-down Saccharomyces cerevisiae cultivation were studied and compared with typical values obtained in homogeneous lab-scale cultivations. While cells were exposed to oscillating substrate and oxygen availability in the scale-down cultivations, growth was reduced and accumulation of carboxylic acids was increased. Sterol synthesis was elevated to ergosterol at the same time. The higher fluxes led to increased concentrations of esterified sterols. The cells thus seem to utilize the increased availability of precursors to fill their sterol reservoirs; however, this seems to be limited in the three-compartment reactor cultivation due to a prolonged exposure to oxygen limitation. Besides, a larger heterogeneity within the single-cell size distribution was observed under oscillatory growth conditions with three-dimensional holographic microscopy. Hence the impact of gradients is also observable at the morphological level. The consideration of such a single-cell-based analysis provides useful information about the homogeneity of responses among the population.

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“…We hypothesize that reduction of the ATPase activity of the importers affects esterification of exogenous sterols and their relocalization to lipid particles. Recent results of Gulati et al (2015) demonstrated tight interaction between sterol import and sterol esterification. Thus, if sterol esterification enzymes (Are2 and Are1) are direct acceptors of the imported sterol from Aus1/Pdr11, their activity can significantly influence efficiency and selectivity of the import.…”

Section: Discussionmentioning

confidence: 99%

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

Papay

Klein

Hapala

et al. 2019

Yeast

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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. K E Y W O R D SABC transporter, anaerobiosis, cholesterol, plant sterols, sterol uptake, yeast

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ATP‐binding cassette transporters and sterol O ‐acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification

Cited by 23 publications

References 55 publications

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2

From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2

Sterol synthesis and cell size distribution under oscillatory growth conditions in Saccharomyces cerevisiae scale‐down cultivations

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

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