Metabolism of the phospholipid precursor inositol and its relationship to growth and viability in the natural auxotroph Schizosaccharomyces pombe

Fernández, S; Homann, Michael J.; Henry, Susan A.; Carman, George M.

doi:10.1128/jb.166.3.779-786.1986

Cited by 37 publications

(41 citation statements)

References 36 publications

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“…Recent experiments have shown that the regulation of general phospholipid mnetabolism in S. pombe is considerably different from regulation in S. cerevisiae (12 (6,10). In contrast, the inositol-requiring yeast S. pombe exhibits a decrease in viability of less than 2 orders of magnitude after 120 h of inositol starvation (7). This increased resistance to inositol starvation may be due to several adaptations in S. pombe phospholipid metabolism.…”

Section: Discussionmentioning

confidence: 86%

“…This increased resistance to inositol starvation may be due to several adaptations in S. pombe phospholipid metabolism. These include a greater increase in the PS/PI ratio in response to inositol starvation and the ability of this organism to recycle inositol (7). A second difference between the two yeasts relates to phospholipid regulation in response to choline.…”

Section: Discussionmentioning

confidence: 99%

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Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline

1991

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The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDP-diacylglycerol glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the committed step in the cardiolipin biosynthetic pathway. To study the regulation of PGPS in Schizosacchlaromyces pombe, we characterized the enzyme biochemically.Maximum activity occurred in the presence of 6 mM Triton X-100 at pH 7.5. The apparent Km values for CDP-diacylglycerol and glycerol 3-phosphate were 130 and 26 ,M, respectively. Optimal activity was at 35°C, and enzyme activity was labile above 40°C. Thioreactive agents were inhibitory to PGPS activity. To determine whether S. pombe PGPS is regulated by phospholipid precursors, we examined the time-dependent expression of PGPS upon inositol and choline starvation. Starvation for inositol resulted in a threefold increase in PGPS expression in wild-type cells. In chol and cho2 mutants, which are blocked in phosphatidylcholine synthesis, starvation for choline resulted in transient derepression of PGPS expression. In choline auxotrophs starved for inositol, PGPS was derepressed 2.5-to 3-fold in the presence of choline and less or not at all in the absence of choline. This is the first description of PGPS regulation in S. pombe and the first demonstration of inositol-mediated regulation in the inositol-requiring yeast species.Inositol plays a crucial role in general phospholipid metabolism in the budding yeast Saccharomyces cerevisiae (3,11,15). In this organism, inositol can be synthesized from glucose 6-phosphate in a reaction catalyzed by inositol 1-phosphate synthase (5). Inositol is utilized in the synthesis of the membrane phospholipid phosphatidylinositol (PI) (Fig. 1) (8). In addition, inositol acts as a regulator of phospholipid synthesis by repressing levels of the PI and phosphatidylcholine (PC) branch enzymes inositol 1-phosphate synthase, CDP-diacylglycerol (CDP-DG) synthase, phosphatidylserine (PS) synthase, PS decarboxylase, and the phospholipid N-methyltransferases (3). Inositol regulation of these enzymes is dependent on PC synthesis as well as the interaction of three unlinked regulatory genes (IN02-IN04-OPII). Choline, which can be used to synthesize PC via the Kennedy pathway, represses inositol 1-phosphate synthase, PS synthase, and the N-methyltransferases, although to a much lesser extent than inositol does. Repression by choline is only apparent in cells grown in the presence of inositol (3,13,21,22).We have made use of the knowledge gained from the genetic and molecular dissection of general phospholipid synthesis to understand how the mitochondrial membrane is synthesized. In S. cerevisiae, the phospholipid cardiolipin (CL) is found only in the mitochondrial membrane and is required for mitochondrial function (14,19). Therefore, we can use this phospholipid as a marker for the study of mitochondrion-specific membrane biogenesis. The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDP-DG sn-glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) is located in the mitochondrial...

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline

1991

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“…Drainas and their total fatty acid composition in S . pombe (White & Hawthorne, 1970;Johnston & Coddington, 1984;Fernadez et al, 1986). The present report gives detailed qualitative and quantitative data on the membrane phospholipids of S .…”

Section: Introductionmentioning

confidence: 99%

Effect of ethanol on the phospholipid and fatty acid content of Schizosaccharomyces pombe membranes

Koukou

Τσουκατοσ²,

Drainas³

1990

Journal of General Microbiology

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~~Ethanol at concentrations up to 5% (v/v) had no effect on the growth of Schizosuccharomycespombe, whereas concentrations over 7.5% were inhibitory. The major membrane phospholipids in S. pombe cells growing aerobically in the absence of added ethanol were phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine. Oleic acid (18:l) was the main fatty acid. When ethanol (7.5%) was added to aerobically growing cultures, the phosphatidylinositol content increased, whereas the 18: 1 content decreased. Similar changes were observed in the membrane phospholipids of cells grown anaerobically without ethanol. However, the presence of ethanol in anaerobically growing cultures had an opposite effect on fatty acids, as the 18: 1 content increased. The results support the idea that ethanol tolerance in S.pombe may be connected with a high content of 18: 1 fatty acids, and with the ability to maintain a high rate of phospholipid biosynthesis.

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“…The membrane phospholipid composition of Schizosaccharomyces pombe is affected by the availability of phospholipid precursors (12,20). In particular, relative amounts of the major anionic phospholipids phosphatidylinositol (PI) and phosphatidylserine (PS) vary in response to the exogenous inositol concentration (12).…”

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confidence: 99%

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confidence: 99%

Regulation of CDP-diacylglycerol synthesis and utilization by inositol and choline in Schizosaccharomyces pombe

Gaynor

Greenberg

1992

J Bacteriol

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CDP-diacylglycerol (CDP-DG (12,20). In particular, relative amounts of the major anionic phospholipids phosphatidylinositol (PI) and phosphatidylserine (PS) vary in response to the exogenous inositol concentration (12). Thus, when the inositol concentration is low, PI content is decreased while PS content is increased. The precursor to the synthesis of PI and PS is CDP-diacylglycerol (CDP-DG) (Fig. 1). This liponucleotide is an important intermediate in yeast phospholipid synthesis, as it is the direct source of the phosphatidyl moiety in phosphatidylglycerolphosphate (PGP), PI, and PS. PGP is then converted to phosphatidylglycerol and cardiolipin, while PS is converted to phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (7). As CDP-DG is located at a crucial branchpoint in phospholipid synthesis, differential regulation of the enzymes which metabolize it may account for the changes in phospholipid composition observed in response to different physiological conditions.In Saccharomyces cerevisiae, the enzymes which synthesize and utilize CDP-DG are regulated on many levels. Inositol is a key regulator of phospholipid biosynthesis in this lower eucaryote (reviewed in references 7 arid 33). The pathway for conversion of phosphatidate, phosphatidate -)

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Metabolism of the phospholipid precursor inositol and its relationship to growth and viability in the natural auxotroph Schizosaccharomyces pombe

Cited by 37 publications

References 36 publications

Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline

Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline

Effect of ethanol on the phospholipid and fatty acid content of Schizosaccharomyces pombe membranes

Regulation of CDP-diacylglycerol synthesis and utilization by inositol and choline in Schizosaccharomyces pombe

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