SUT1 is a putative Zn[II]2Cys6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomycescerevisiae cells

Budding yeast Saccharomyces cerevisiae is a facultative anaerobe whose grow th upon oxygen starvation depends on its capacity to import exogenously sup plied sterols, whereas the cells are not permeable to these molecules when grown aerobically. Few genes have been identified as being involved in ster ol uptake. A higher SUT1 gene dosage leads to a modest, but significant, in crease in sterol uptake under aerobic conditions. Based on sequence and phy siological data, SUT1 is a hypoxic gene negatively regulated when the cells are grown in the presence of oxygen. We replaced the SUT1 promoter with th e constitutive PMA1 gene promoter in order to enhance its transcription. We observed that sterol uptake was then comparable with that obtained with a sterol importing hem1 mutant, although the heme status of the strain was no t modified in a process which still occurs when the cells are not growing. Unexpectedly, SUT1 constitutive expression led to a parallel significant in crease in endogenous sterol biosynthesis. Moreover, here we present new dat a showing that the structurally related YPR009 gene (SUT2) is a functional homologue of SUT1, and that both gene products may represent two novel yeas t regulatory proteins involved in sterol uptake.