Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast

TY - JOUR

T1 - Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast

AU - Marek, Magdalena

AU - Silvestro, Daniele

AU - Fredslund, Maria D.

AU - Andersen, Tonni G.

AU - Günther-Pomorski, Thomas

PY - 2014

Y1 - 2014

N2 - 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. Serum albumin can serve as sterol donor in ATP-binding cassette-transporter-dependent sterol uptake, a process potentially important for growth of Candida glabrata inside infected humans.

AB - 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. Serum albumin can serve as sterol donor in ATP-binding cassette-transporter-dependent sterol uptake, a process potentially important for growth of Candida glabrata inside infected humans.

KW - Aerobic exclusion

KW - Cholesterol

KW - Functional complementation

KW - Heterologous expression

KW - Pathogenic yeast

KW - Sterol scavenging

U2 - 10.1111/1567-1364.12219

DO - 10.1111/1567-1364.12219

M3 - Journal article

C2 - 25331273

AN - SCOPUS:84918570037

SN - 1567-1356

VL - 14

SP - 1223

EP - 1233

JO - FEMS Yeast Research

JF - FEMS Yeast Research

IS - 8

ER -