Transcriptional Regulation by Ergosterol in the Yeast Saccharomyces cerevisiae

Abstract

Sterol biosynthesis in the yeast Saccharomyces cerevisiae is an energy-expensive, aerobic process, requiring heme and molecular oxygen. Heme, also synthesized exclusively during aerobic growth, not only acts as an enzymatic cofactor but also is directly and indirectly responsible for the transcriptional control of several yeast genes. Because of their biosynthetic similarities, we hypothesized that ergosterol, like heme, may have a regulatory function. Sterols are known to play a structural role in membrane integrity, but regulatory roles have not been characterized. To test possible regulatory roles of sterol, the promoter for the ERG3 gene, encoding the sterol C-5 desaturase, was fused to the bacterial lacZ reporter gene. This construct was placed in strains making aberrant sterols, and the effect of altered sterol composition on gene expression was monitored by ␤-galactosidase activity. The absence of ergosterol resulted in a 35-fold increase in the expression of ERG3 as measured by ␤-galactosidase activity. The level of ERG3 mRNA was increased as much as ninefold in erg mutant strains or wild-type strains inhibited in ergosterol biosynthesis by antifungal agents. The observed regulatory effects of ergosterol on ERG3 are specific for ergosterol, as several ergosterol derivatives failed to elicit the same controlling effect. These results demonstrate for the first time that ergosterol exerts a regulatory effect on gene transcription in S. cerevisiae. Ergosterol (Fig.

Modulation of Geraniol Metabolism During Alcohol Fermentation

“…Also ergosterol can have a regulating effect on yeast sterol metabolism 18 . The level of ergosterol was shown to regulate the transcription of Erg 3, a codified gene for the C 5 -desaturase which catalyses the saturation reaction C 5 -C 6 of the molecule.…”

Decrease of H2O2 Plasma Membrane Permeability during Adaptation to H2O2 in Saccharomyces cerevisiae

“…This decrease is similar to that observed when cells are exposed to an adaptive of two Sc strains, which have defective membranes, with that of the wild type Sc strain. The two strains used (erg3⌬ and erg6⌬) have a defect in the pathway of ergosterol biosynthesis: erg3⌬ mutants lack a C-5 desaturase producing ergosta-7,22-dienol instead of ergosterol (31), and erg6⌬ mutants lack a C-24 methyltransferase producing zymosterol and colesta-5,7,24-trienol instead of ergosterol (32). In both mutants the membrane biophysical properties are changed, resulting in increased permeability to lipophilic compounds (9).…”

“…tase (8), the rate-limiting enzyme in the ergosterol biosynthesis pathway; (b) H 2 O 2 inhibits the enzyme HMG-CoA reductase (33); (c) cycloheximide, a protein synthesis inhibitor that can possibly lead to a lower steady state level of HMG-CoA reductase, decreases plasma membrane permeability to H 2 O 2 (this work); and (d) erg3⌬ and erg6⌬, which accumulate altered sterols (9) and have the ergosterol biosynthesis pathway up-regulated (31,34), show increased permeability to H 2 O 2 (this work).…”

A Role for Sterol Levels in Oxygen Sensing in Saccharomyces cerevisiae

“…Regulation of ergosterol in Saccharomyces cerevisiae has both intrinsic and practical interest as this pathway contains the targets of most antifungal drugs. Genes encoding enzymes of ergosterol biosynthesis are transcriptionally regulated in response to the need for ergosterol (Arthington-Skaggs et al 1996;DimsterDenk and Rine 1996;Smith et al 1996;Kennedy et al 1999) but in ways that differ markedly from the regulation of the corresponding genes in mammals (Dimster-Denk and Rine 1996; Davies et al 2005).…”