The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
George M. Carman - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidate phosphatase regulates membrane Phospholipid Synthesis via phosphatidylserine synthase.
Advances in biological regulation, 2017Co-Authors: George M. Carman, Gil-soo HanAbstract:Abstract The yeast Saccharomyces cerevisiae serves as a model eukaryote to elucidate the regulation of lipid metabolism. In exponentially growing yeast, a diverse set of membrane lipids are synthesized from the precursor phosphatidate via the liponucleotide intermediate CDP-diacylglycerol. As cells exhaust nutrients and progress into the stationary phase, phosphatidate is channeled via diacylglycerol to the Synthesis of triacylglycerol. The CHO1 -encoded phosphatidylserine synthase, which catalyzes the committed step in membrane Phospholipid Synthesis via CDP-diacylglycerol, and the PAH1 -encoded phosphatidate phosphatase, which catalyzes the committed step in triacylglycerol Synthesis are regulated throughout cell growth by genetic and biochemical mechanisms to control the balanced Synthesis of membrane Phospholipids and triacylglycerol. The loss of phosphatidate phosphatase activity (e.g., pah1 Δ mutation) increases the level of phosphatidate and its conversion to membrane Phospholipids by inducing Cho1 expression and phosphatidylserine synthase activity. The regulation of the CHO1 expression is mediated through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. Consequently, phosphatidate phosphatase activity regulates Phospholipid Synthesis through the transcriptional regulation of the phosphatidylserine synthase enzyme.
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Phospholipid Synthesis in Yeast
Encyclopedia of Biological Chemistry, 2013Co-Authors: Gil-soo Han, George M. CarmanAbstract:Phospholipids are essential molecules that contribute to the structural definition of the cell. They also play a role as signaling molecules that participate in the regulation of cellular processes. The yeast Saccharomyces cerevisiae has been used as a model system to study Phospholipid Synthesis and its regulation in eukaryotes. Molecular, genetic, and biochemical studies have shown that Phospholipid Synthesis is regulated in a coordinated fashion. The mechanisms that govern this regulation mediate the messenger RNA and protein levels of the biosynthetic enzymes, as well as their activity and localization.
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Regulation of Phospholipid Synthesis in the Yeast Saccharomyces cerevisiae
Annual review of biochemistry, 2011Co-Authors: George M. Carman, Gil-soo HanAbstract:The yeast Saccharomyces cerevisiae, with its full complement of organelles, synthesizes membrane Phospholipids by pathways that are generally common to those found in higher eukaryotes. Phospholipid Synthesis in yeast is regulated in response to a variety of growth conditions (e.g., inositol supplementation, zinc depletion, and growth stage) by a coordination of genetic (e.g., transcriptional activation and repression) and biochemical (e.g., activity modulation and localization) mechanisms. Phosphatidate (PA), whose cellular levels are controlled by the activities of key Phospholipid Synthesis enzymes, plays a central role in the transcriptional regulation of Phospholipid Synthesis genes. In addition to the regulation of gene expression, phosphorylation of key Phospholipid Synthesis catalytic and regulatory proteins controls the metabolism of Phospholipid precursors and products.
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dgk1 encoded diacylglycerol kinase activity is required for Phospholipid Synthesis during growth resumption from stationary phase in saccharomyces cerevisiae
Journal of Biological Chemistry, 2011Co-Authors: Stylianos Fakas, Chrysanthos Konstantinou, George M. CarmanAbstract:In the yeast Saccharomyces cerevisiae, triacylglycerol mobilization for Phospholipid Synthesis occurs during growth resumption from stationary phase, and this metabolism is essential in the absence of de novo fatty acid Synthesis. In this work, we provide evidence that DGK1-encoded diacylglycerol kinase activity is required to convert triacylglycerol-derived diacylglycerol to phosphatidate for Phospholipid Synthesis. Cells lacking diacylglycerol kinase activity (e.g. dgk1Δ mutation) failed to resume growth in the presence of the fatty acid Synthesis inhibitor cerulenin. Lipid analysis data showed that dgk1Δ mutant cells did not mobilize triacylglycerol for membrane Phospholipid Synthesis and accumulated diacylglycerol. The dgk1Δ phenotypes were partially complemented by preventing the formation of diacylglycerol by the PAH1-encoded phosphatidate phosphatase and by channeling diacylglycerol to phosphatidylcholine via the Kennedy pathway. These observations, coupled to an inhibitory effect of dioctanoyl-diacylglycerol on the growth of wild type cells, indicated that diacylglycerol kinase also functions to alleviate diacylglycerol toxicity.
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Regulation of Phospholipid Synthesis in yeast.
Journal of lipid research, 2008Co-Authors: George M. Carman, Gil-soo HanAbstract:Phospholipid Synthesis in the yeast Saccharomyces cerevisiae is a complex process that involves regulation by both genetic and biochemical mechanisms. The activity levels of Phospholipid Synthesis enzymes are controlled by gene expression (e.g., transcription) and by factors (lipids, water-soluble Phospholipid precursors and products, and covalent modification of phosphorylation) that modulate catalysis. Phosphatidic acid, whose levels are controlled by the biochemical regulation of key Phospholipid Synthesis enzymes, plays a central role in the regulation of Phospholipid Synthesis gene expression.
Gil-soo Han - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidate phosphatase regulates membrane Phospholipid Synthesis via phosphatidylserine synthase.
Advances in biological regulation, 2017Co-Authors: George M. Carman, Gil-soo HanAbstract:Abstract The yeast Saccharomyces cerevisiae serves as a model eukaryote to elucidate the regulation of lipid metabolism. In exponentially growing yeast, a diverse set of membrane lipids are synthesized from the precursor phosphatidate via the liponucleotide intermediate CDP-diacylglycerol. As cells exhaust nutrients and progress into the stationary phase, phosphatidate is channeled via diacylglycerol to the Synthesis of triacylglycerol. The CHO1 -encoded phosphatidylserine synthase, which catalyzes the committed step in membrane Phospholipid Synthesis via CDP-diacylglycerol, and the PAH1 -encoded phosphatidate phosphatase, which catalyzes the committed step in triacylglycerol Synthesis are regulated throughout cell growth by genetic and biochemical mechanisms to control the balanced Synthesis of membrane Phospholipids and triacylglycerol. The loss of phosphatidate phosphatase activity (e.g., pah1 Δ mutation) increases the level of phosphatidate and its conversion to membrane Phospholipids by inducing Cho1 expression and phosphatidylserine synthase activity. The regulation of the CHO1 expression is mediated through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2–Ino4/Opi1) regulatory circuit. Consequently, phosphatidate phosphatase activity regulates Phospholipid Synthesis through the transcriptional regulation of the phosphatidylserine synthase enzyme.
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Phospholipid Synthesis in Yeast
Encyclopedia of Biological Chemistry, 2013Co-Authors: Gil-soo Han, George M. CarmanAbstract:Phospholipids are essential molecules that contribute to the structural definition of the cell. They also play a role as signaling molecules that participate in the regulation of cellular processes. The yeast Saccharomyces cerevisiae has been used as a model system to study Phospholipid Synthesis and its regulation in eukaryotes. Molecular, genetic, and biochemical studies have shown that Phospholipid Synthesis is regulated in a coordinated fashion. The mechanisms that govern this regulation mediate the messenger RNA and protein levels of the biosynthetic enzymes, as well as their activity and localization.
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Regulation of Phospholipid Synthesis in the Yeast Saccharomyces cerevisiae
Annual review of biochemistry, 2011Co-Authors: George M. Carman, Gil-soo HanAbstract:The yeast Saccharomyces cerevisiae, with its full complement of organelles, synthesizes membrane Phospholipids by pathways that are generally common to those found in higher eukaryotes. Phospholipid Synthesis in yeast is regulated in response to a variety of growth conditions (e.g., inositol supplementation, zinc depletion, and growth stage) by a coordination of genetic (e.g., transcriptional activation and repression) and biochemical (e.g., activity modulation and localization) mechanisms. Phosphatidate (PA), whose cellular levels are controlled by the activities of key Phospholipid Synthesis enzymes, plays a central role in the transcriptional regulation of Phospholipid Synthesis genes. In addition to the regulation of gene expression, phosphorylation of key Phospholipid Synthesis catalytic and regulatory proteins controls the metabolism of Phospholipid precursors and products.
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Regulation of Phospholipid Synthesis in yeast.
Journal of lipid research, 2008Co-Authors: George M. Carman, Gil-soo HanAbstract:Phospholipid Synthesis in the yeast Saccharomyces cerevisiae is a complex process that involves regulation by both genetic and biochemical mechanisms. The activity levels of Phospholipid Synthesis enzymes are controlled by gene expression (e.g., transcription) and by factors (lipids, water-soluble Phospholipid precursors and products, and covalent modification of phosphorylation) that modulate catalysis. Phosphatidic acid, whose levels are controlled by the biochemical regulation of key Phospholipid Synthesis enzymes, plays a central role in the regulation of Phospholipid Synthesis gene expression.
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Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by zinc depletion.
Biochimica et biophysica acta, 2006Co-Authors: George M. Carman, Gil-soo HanAbstract:The Synthesis of Phospholipids in the yeast Saccharomyces cerevisiae is regulated by zinc, an essential mineral required for growth and metabolism. Cells depleted of zinc contain increased levels of phosphatidylinositol and decreased levels of phosphatidylethanolamine. In addition to the major Phospholipids, the levels of the minor Phospholipids phosphatidate and diacylglycerol pyrophosphate decrease in the vacuole membrane of zinc-depleted cells. Alterations in phosphatidylinositol and phosphatidylethanolamine can be ascribed to an increase in PIS1-encoded phosphatidylinositol synthase activity and to decreases in the activities of CDP-diacylglycerol pathway enzymes including the CHO1-encoded phosphatidylserine synthase, respectively. Alterations in the minor vacuole membrane Phospholipids are due to the induction of the DPP1-encoded diacylglycerol pyrophosphate phosphatase. These changes in the activities of Phospholipid biosynthetic enzymes result from differential regulation of gene expression at the level of transcription. Under zinc-deplete conditions, the positive transcription factor Zap1p stimulates the expression of the DPP1 and PIS1 genes through the cis-acting element UASZRE. In contrast, the negative regulatory protein Opi1p, which is involved in inositol-mediated regulation of Phospholipid Synthesis, represses the expression of the CHO1 gene through the cis-acting element UASINO. Regulation of Phospholipid Synthesis may provide an important mechanism by which cells cope with the stress of zinc depletion, given the roles that Phospholipids play in the structure and function of cellular membranes.
Martin Graef - One of the best experts on this subject based on the ideXlab platform.
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Localized de novo Phospholipid Synthesis drives autophagosome biogenesis.
Autophagy, 2020Co-Authors: Maximilian Schütter, Martin GraefAbstract:During (macro)autophagy, cells form transient organelles, termed autophagosomes, to target a broad spectrum of substrates for degradation critical to cellular and organismal health. Driven by rapid membrane assembly, an initially small vesicle (phagophore) elongates into a large cup-shaped structure to engulf substrates within a few minutes in a double-membrane autophagosome. In particular, how autophagic membranes expand has been a longstanding question. Here, we summarize our recent work that delineates a pathway that drives phagophore expansion by localized de novo Phospholipid Synthesis. Specifically, we found that the conserved acyl-CoA synthetase Faa1 localizes to nucleated phagophores to locally activate fatty acids for de novo Phospholipid Synthesis in the neighboring ER. These newly synthesized Phospholipids are then preferentially incorporated into autophagic membranes and drive the expansion of the phagophore into a functional autophagosome. In summary, our work uncovers molecular principles of how cells coordinate Phospholipid Synthesis and flux with autophagic membrane formation during autophagy.Abbreviations: ACS: acyl-CoA synthestases; CoA: coenzyme A; ER: endoplasmic reticulum.
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local fatty acid channeling into Phospholipid Synthesis drives phagophore expansion during autophagy
Cell, 2020Co-Authors: Maximilian Schütter, Martin Graef, Patrick Giavalisco, Susanne BrodesserAbstract:Summary Autophagy is a conserved catabolic homeostasis process central for cellular and organismal health. During autophagy, small single-membrane phagophores rapidly expand into large double-membrane autophagosomes to encapsulate diverse cargoes for degradation. It is thought that autophagic membranes are mainly derived from preformed organelle membranes. Instead, here we delineate a pathway that expands the phagophore membrane by localized Phospholipid Synthesis. Specifically, we find that the conserved acyl-CoA synthetase Faa1 accumulates on nucleated phagophores and locally activates fatty acids (FAs) required for phagophore elongation and autophagy. Strikingly, using isotopic FA tracing, we directly show that Faa1 channels activated FAs into the Synthesis of Phospholipids and promotes their assembly into autophagic membranes. Indeed, the first committed steps of de novo Phospholipid Synthesis at the ER, which forms stable contacts with nascent autophagosomes, are essential for autophagy. Together, our work illuminates how cells spatially tune Synthesis and flux of Phospholipids for autophagosome biogenesis during autophagy.
France Van Wambeke - One of the best experts on this subject based on the ideXlab platform.
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Phospholipid Synthesis rates in the eastern subtropical South Pacific Ocean
Biogeosciences, 2008Co-Authors: B. A. S. Van Mooy, T. Moutin, S. Duhamel, P. Rimmelin, France Van WambekeAbstract:Membrane lipid molecules are a major component of planktonic organisms and this is particularly true of the microbial picoplankton that dominate the open ocean; with their high surface-area to volume ratios, the Synthesis of membrane lipids places a major demand on their overall cell metabolism. Specifically, the Synthesis of cell membrane Phospholipids creates a demand for the nutrient phosphorus, and we sought to refine our understanding of the role of Phospholipids in the upper ocean phosphorus cycle. We measured the rates of Phospholipid Synthesis in a transect of the eastern subtropical South Pacific from Easter Island to Concepcion, Chile as part of the BIOSOPE program. Our approach combined standard phosphorus radiotracer incubations and lipid extraction methods. We found that Phospholipid Synthesis rates varied from less than 1 to greater than 200 pmol P L-1 h-1, and that Phospholipid Synthesis contributed between less than 5% to greater than 22% of the total PO43- incorporation rate. Changes in the percentage that Phospholipid Synthesis contributed to total PO43- uptake were strongly correlated with the ratio of primary production to bacterial production, which supported our hypothesis that heterotrophic bacteria were the primary agents of Phospholipid Synthesis. The spatial variation in Phospholipid Synthesis rates underscored the importance of heterotrophic bacteria in the phosphorus cycle of the eastern subtropical South Pacific, particularly the hyperoligotrophic South Pacific subtropical gyre.
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Phospholipid Synthesis rates in the eastern subtropical South Pacific Ocean
Biogeosciences Discussions, 2007Co-Authors: B. A. S. Van Mooy, T. Moutin, S. Duhamel, P. Rimmelin, France Van WambekeAbstract:Membrane lipid molecules are a major component of planktonic organisms and this is particularly true of the microbial picoplankton that dominate the open ocean; with their high surface-area to volume ratios, the Synthesis of membrane lipids places a major demand on their overall cell metabolism. The Synthesis of one class of membrane lipids, the Phospholipids, also creates a demand for the nutrient phosphorus, and we sought to refine our understanding of the role of Phospholipids in the upper ocean phosphorus cycle. We measured the rates of Phospholipid Synthesis in a transect of the eastern subtropical South Pacific from Easter Island to Concepcion, Chile as part of the BIOSOPE program. Our approach combined standard phosphorus radiotracer incubations and lipid extraction methods. We found that Phospholipid Synthesis rates varied from less than 1 to greater than 200 pmol P L-1 h-1, and that Phospholipid Synthesis contributed between less than 5% to greater than 22% of the total PO43- incorporation rate. Changes in the percentage that Phospholipid Synthesis contributed to total PO43- incorporation were strongly correlated with the ratio of primary production to bacterial production, which supported our hypothesis that heterotrophic bacteria were the primary agents of Phospholipid Synthesis. The spatial variation in Phospholipid Synthesis rates underscored the importance of heterotrophic bacteria in the phosphorus cycle of the eastern subtropical South Pacific, particularly the hyperoligotrophic South Pacific subtropical gyre.
Daniel J. Klionsky - One of the best experts on this subject based on the ideXlab platform.
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As (and when) you like it: on-demand Phospholipid Synthesis drives phagophore expansion during autophagy.
Autophagy, 2020Co-Authors: Shree Padma Metur, Daniel J. KlionskyAbstract:A key feature of macroautophagy/autophagy is the formation of a transient de novo compartment called the phagophore, which envelops cytoplasmic material, ultimately enclosing it within an autophagosome, allowing it to be targeted for degradation. Schutter et al describe a novel mechanism that spatiotemporally coordinates Phospholipid Synthesis to drive phagophore expansion and autophagosome formation. These authors show that during starvation, fatty acids (FAs) are channeled into Phospholipid Synthesis, and the newly synthesized lipids are directed toward autophagosome biogenesis.Abbreviations: ACS: acyl-CoA synthetase; ER: endoplasmic reticulum; FA: fatty acid; FAS: fatty acid synthetase; MCS: membrane contact sites; PAS: phagophore assembly site.