Disease relevance of PGS1

• A partial homology in primary structures was noticed between this yeast enzyme and phosphatidylglycerophosphate synthase of Escherichia coli which also uses CDP-diacylglycerol as a substrate [1].

High impact information on PGS1

• Reintroduction of a functional PGS1 gene under control of the ADH1 promoter restored phosphatidylglycerol synthesis and expression of mtGFP [2].
• Therefore, the role of Pgs1p in activation of Isc1p in vivo was investigated [3].
• Disruption of PGS1, which encodes the enzyme that catalyzes the committed step of cardiolipin (CL) synthesis, results in loss of the mitochondrial anionic phospholipids phosphatidylglycerol (PG) and CL [4].
• Growth in the presence of the inositol-depleting drug valproate led to an increase in phosphatidylglycerophosphate synthase activity unaccompanied by increased PGS1 mRNA [5].
• PGS1 was increased in glycerol/ethanol compared with glucose media and was maximally expressed as cells entered the stationary phase [5].

Chemical compound and disease context of PGS1

• The E. coli pgsA gene encodes phosphatidylglycerophosphate synthase (PGPS), catalyzing the first step in the CL biosynthetic pathway [6].

Biological context of PGS1

• Deletion of the mitochondrial genome did not affect PGS1 expression [5].
• The molecular mechanism of this regulation was examined by using a reporter gene under control of the PGS1 gene promoter (PPGS1-lacZ) [7].
• The PEL1-GFP fusion gene has been found to complement the pel1/pgs1 mutation and its fluorescent protein was localized to mitochondria similarly to the beta-galactosidase activity of a protein encoded by the PEL1-lacZ fusion gene [8].
• Disruption of the PGS1 gene in a haploid strain of yeast did not lead to a loss of viability but did result in a dependence on a fermentable carbon source for growth, a temperature sensitivity for growth, and a petite lethal phenotype [9].
• These results unequivocally demonstrate that the PGS1 gene encodes the major PG-P synthase of yeast and that neither PG nor CL are absolutely essential for cell viability but may be important for normal mitochondrial function [9].

Anatomical context of PGS1

• The results demonstrate that Pel1p, playing a vital role in cells impaired in the mitochondrial DNA, is localized in the mitochondria and expressed in response to inositol and choline [8].
• Furthermore, overexpression of hCLS1 cDNA in COS-7 cells resulted in a significant increase in cardiolipin synthesis in intact COS-7 cells without any significant effects on the activity of the endogenous phosphatidylglycerophosphate synthase of the transfected COS-7 cells [10].

Associations of PGS1 with chemical compounds

• The addition of increasing concentrations of doxycycline to the growth medium causes a proportional decrease to undetectable levels of PGS1 transcript, PG phosphate synthase activity, and PG plus CL [11].
• We report here that steady state mRNA levels of the PGS1 gene, which encodes phosphatidylglycerophosphate synthase, were not altered by inositol or choline [5].
• Disruption of the PEL1 gene was not lethal and resulted in the same phenotype as observed with the pel1 mutant, i.e. the cells were not able to survive ethidium bromide mutagenesis, were thermosensitive for growth on glucose at 37 degrees C and failed to grow on minimal glycerol medium [12].
• In cells starved for inositol, this decrease in PGP synthase, PI synthase, and PS synthase expression was not observed [13].
• The PEL1 gene of Saccharomyces cerevisiae is essential for the cell viability of mitochondrial petite mutants, for the ability to utilize glycerol and ethanol on synthetic medium, and for cell growth at higher temperatures [14].

Other interactions of PGS1

• Overexpression of the PGS1 gene product under the inducible GAL1 promoter resulted in a 14-fold increase in in vitro PG-P synthase activity [9].
• Interestingly, CL synthesis increased in the mutant, whereas expression of the CL structural genes CRD1 and PGS1 did not, suggesting that de novo biosynthetic enzyme activities are regulated by CL acylation [15].
• Molecular characterization of the PEL1 gene encoding a putative phosphatidylserine synthase [12].
• Starvation for inositol resulted in a twofold derepression of PGP synthase and PS synthase expression, while PI synthase expression decreased initially and then remained constant [13].

Analytical, diagnostic and therapeutic context of PGS1

• The size of the PEL1 transcript in Northern blot analysis was estimated to be approximately 1.5 kb [12].
• Molecular cloning of the PEL1 gene of Saccharomyces cerevisiae that is essential for the viability of petite mutants [14].

References