Biomedical subjects

S Tove

Publications and source records attributed to S Tove.

5 recordsLinked to original sources

PubMed1999

In yeast, upc2-1 confers a decrease in tolerance to LiCl and NaCl, which can be suppressed by the P-type ATPase encoded by ENA2.

Wild-type yeast cells are unable to take up sterols from their growth media under aerobic conditions and are relatively resistant to monovalent cations. A yeast mutant (upc2-1) with a defect in the aerobic exclusion of sterols was found to have increased sensitivity to LiCl and NaCl. Although cation sensitivity has been reported for mutants that synthesize altered sterols, the mutant with upc2-1 continues to produce the normal sterol, ergosterol. The ENA2 gene was cloned on the basis of remediating the hypersensitivity to the monovalent cations.

Adenosine Triphosphatases↗

PubMed1998

A calcium-dependent ergosterol mutant of Saccharomyces cerevisiae.

ERG24 is the structural gene for the C14-sterol reductase in yeast. A lack of activity in that enzyme, mediated either by the morpholine fungicides or the insertional inactivation of ERG24, causes the accumulation of the aberrant sterol ignosterol. Cells producing this sterol are unable to grow aerobically in the routine laboratory medium, YPD. However, growth does occur on a synthetic defined medium. A novel calcium-dependent phenotype associated with alterations in the ergosterol biosynthetic pathway in yeast is described. In addition, reduction of yeast growth with an azole inhibitor of the C-14 sterol de-methylase was also modulated by an excess of calcium ions in the culture medium. These results define a new effect of ergosterol deficiency and provide important practical implications for utilizing morpholine and azole sterol biosynthetic-inhibiting fungicides.

Antifungal Agents↗

PubMed1998

A mutation in a purported regulatory gene affects control of sterol uptake in Saccharomyces cerevisiae.

Aerobically growing wild-type strains of Saccharomyces cerevisiae are unable to take exogenously supplied sterols from media. This aerobic sterol exclusion is vitiated under anaerobic conditions, in heme-deficient strains, and under some conditions of impaired sterol synthesis. Mutants which can take up sterols aerobically in heme-competent cells have been selected. One of these mutations, designated upc2-1, gives a pleiotropic phenotype in characteristics as diverse as aerobic accumulation of sterols, total lipid storage, sensitivity to metabolic inhibitors, response to altered sterol structures, and cation requirements. During experiments designed to ascertain the effects of various cations on yeast with sterol alterations, it was observed that upc2-1 was hypersensitive to Ca2+. Using resistance to Ca2+ as a screening vehicle, we cloned UPC2 and showed that it is YDR213W, an open reading frame on chromosome IV. This belongs to a fungal regulatory family containing the Zn(II)2Cys6 binuclear cluster DNA binding domain. The single guanine-to-adenine transition in upc2-1 gives a predicted amino acid change from glycine to aspartic acid. The regulatory defect explains the semidominance and pleiotropic effects of upc2-1.

Amino Acid Sequence↗

PubMed1997

A conditional sterol esterification defect in yeast having either a sec1 or sec5 mutation in the secretory pathway.

Two temperature-conditional secretory mutations, sec1 and sec5, cause the accumulation of post-Golgi vesicles when strains containing these mutations are grown at 37 degrees C. In addition to accumulating vesicles, the mutants do not esterify free sterol on rich media at the restrictive temperature. It is the high level of inositol in the media that causes this condition in the yeast Saccharomyces cerevisiae, not a defective steryl ester synthase or lack of substrates. When strains containing the sec1 or sec5 mutation were transformed separately with a plasmid carrying SEC1 and SEC5, the esterification and secretory defects were alleviated. Double mutants containing sec6, sec14 or sec18 with either a sec1 or sec5 mutation have normal esterification levels. Strains with suppressor mutations were isolated that grew at 37 degrees C, esterified sterols and had diminished accumulation of vesicles, when grown at the restrictive temperature on defined media with additional inositol. Electron microscopy was used to examine vesicle accumulation, the number of lipid droplets, and to further characterize the esterification defect. When grown at 37 degrees C on defined medium, the strains with sec5 or sec1 accumulated the usual secretory vesicles, but when grown under similar conditions with elevated levels of inositol, accumulated an additional vesicular-like body.

Esterification↗

PubMed1997

Assessment of the essentiality of ERG genes late in ergosterol biosynthesis in Saccharomyces cerevisiae.

Isogenic strains of yeast were constructed, differing only in insertionally inactivated genes for ergosterol biosynthesis. These and their allelic wild-types were grown in competition to ascertain growth differences and any selective advantage for organisms producing sterols with or without specific features of ergosterol. In every instance tested, the wild-type allele afforded a competitive advantage over the isogenic pair producing modified sterol structures instead of ergosterol. A general trend was seen in which the earlier in the biosynthetic pathway that a mutation occurred, the less able the strain producing the defective sterols could compete with the ergosterol-producing strains.

3-Isopropylmalate Dehydrogenase↗