title: Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast.
abstract: Sterol uptake in fungi is a multistep process that involves interaction between external sterols and the cell wall, incorporation of sterol molecules into the plasma membrane, and subsequent integration into intracellular membranes for turnover. ATP-binding cassette (ABC) transporters have been implicated in sterol uptake, but key features of their activity remain to be elucidated. Here, we apply fluorescent cholesterol (NBD-cholesterol) to monitor sterol uptake under anaerobic and aerobic conditions in two fungal species, Candida glabrata (Cg) and Saccharomyces cerevisiae (Sc). We found that in both fungal species, ABC transporter-dependent uptake of cholesterol under anaerobic conditions and in mutants lacking HEM1 gene is promoted in the presence of the serum protein albumin that is able to bind the sterol molecule. Furthermore, the C. glabrata ABC transporter CgAus1p expressed in S. cerevisiae requires the presence of serum or albumin for efficient cholesterol uptake. These results suggest that albumin can serve as sterol donor in ABC transporter-dependent sterol uptake, a process potentially important for growth of C. glabrata inside infected humans.
authors.affiliation: Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Marek
authors.forename: Daniele
authors.initials: D
authors.lastname: Silvestro
authors.forename: Maria D
authors.initials: MD
authors.lastname: Fredslund
authors.forename: Tonni G
authors.initials: TG
authors.lastname: Andersen
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Pomorski
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000332:Aerobiosis; D000693:Anaerobiosis; D001692:Biological Transport; D041221:Candida glabrata / Q000378:metabolism*; D005453:Fluorescence; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D013194:Staining and Labeling; D013261:Sterols / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D012709:Serum Albumin; D013261:Sterols
keywords: aerobic exclusion; cholesterol; functional complementation; heterologous expression; pathogenic yeast; sterol scavenging