scholarly journals Local Fatty Acid Channeling into Phospholipid Synthesis Drives Phagophore Expansion during Autophagy

Cell ◽  
2020 ◽  
Vol 180 (1) ◽  
pp. 135-149.e14 ◽  
Author(s):  
Maximilian Schütter ◽  
Patrick Giavalisco ◽  
Susanne Brodesser ◽  
Martin Graef
1980 ◽  
Vol 58 (7) ◽  
pp. 527-533 ◽  
Author(s):  
P. J. A. O'Doherty

The effects of ethanolamine, choline, and different fatty acids on phospholipid synthesis via the CDP-ester pathways were studied in isolated rat intestinal villus cells. The incorporation of [14C]glucose into phosphatidylethanolamine was stimulated severalfold by the addition of ethanolamine and long-chained unsaturated fatty acids, while the addition of lauric acid inhibited the incorporation of radioactivity into phosphatidylethanolamine. At concentrations of ethanolamine higher than 0.2 mM, phosphoethanolamine accumulated, but the concentration of CDP-ethanolamine and the incorporation of radioactivity into phosphatidylethanolamine did not increase further. The incorporation of [14C]glucose into phosphatidylcholine responded in a way similar to that of phosphatidylethanolamine, except that a 10-fold higher concentration of choline was required for maximal stimulation. CCC inhibited the incorporation of choline into phosphatidylcholine. In contrast with hepatocytes, villus cells did not form phosphatidylcholine via phospholipid N-methylation. The data indicate that, in intestinal villus cells, the cytidylyltransferase reactions are rate limiting in the synthesis of phosphatidylethanolamine and probably also of phosphatidylcholine. The availability of diacylglycerol and its fatty acid composition may also significantly affect the rate of phospholipid synthesis.


2010 ◽  
Vol 163 ◽  
pp. S29
Author(s):  
Josef Ecker ◽  
Gerhard Liebisch ◽  
Marion Englmaier ◽  
Margot Grandl ◽  
Horst Robenek ◽  
...  

1968 ◽  
Vol 110 (4) ◽  
pp. 49P-50P ◽  
Author(s):  
M I Gurr ◽  
M P Robinson ◽  
R W Sword ◽  
A T James

1984 ◽  
Vol 62 (6) ◽  
pp. 375-378 ◽  
Author(s):  
Pierre Leblanc ◽  
Gerhard E. Gerber

The photoreactive ω-diazirinophenoxy derivatives of nonanoate, undecanoate, tridecanoate, and pentadecanoate were shown to be activated by rat liver microsomes to the corresponding acyl-CoA derivatives. The Km and Vmax for these fatty acid analogues were determined; the values obtained indicate that the addition of a photoreactive group to an alkyl chain has an effect similar to that of elongation of the chain by about seven carbons. Incubation of microsomes in the presence of lysophospholipids resulted in the incorporation of the photoreactive fatty acids into the corresponding phospholipids. The ability of mammalian systems to utilize these photoreactive fatty acids for phospholipid synthesis establishes their suitability as photoaffinity analogues of fatty acids.


2021 ◽  
Author(s):  
Sumie Eto ◽  
Rumie Matsumura ◽  
Mai Fujimi ◽  
Yasuhiro Shimane ◽  
Samuel Berhanu ◽  
...  

Phospholipid synthesis is a fundamental process that promotes cell propagation and, presently, is the most challenging issue in artificial cell research aimed at reconstituting living cells from biomolecules. Here, we constructed a cell-free phospholipid synthesis system that combines in vitro fatty acid synthesis and a cell-free gene expression system that synthesizes acyltransferases for phospholipid synthesis. Fatty acids were synthesized from acetyl-CoA and malonyl-CoA, then continuously converted into phosphatidic acids by the cell-free synthesized acyltransferases. Because the system can avoid the accumulation of synthetic intermediates that suppress the reaction, the yield of phospholipid has significantly improved from previous schemes (up to 400 μM). Additionally, by adding enzymes for recycling CoA, we synthesized phosphatidic acids from acetic acid and bicarbonate as carbon sources. The constructed system is available to express the genes from pathogenic bacteria and to analyze the synthesized phospholipids. By encapsulating our system inside giant vesicles, it would be possible to construct the artificial cells in which the membrane grows and divides sustainably.


2019 ◽  
Author(s):  
Marek J Noga ◽  
Ferhat Büke ◽  
Niels JF van den Broek ◽  
Nicole Imholz ◽  
Nicole Scherer ◽  
...  

AbstractEvery cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyses the committed step of lipopolysaccharide synthesis (LpxC) do not vary across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we find that responses to environmental perturbations are triggered directly via changes in acetyl-CoA concentrations, which enables rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon post-translational regulation ensures both reliability and responsiveness of membrane synthesis.SignificanceHow do bacteria cells grow without breaking their membranes? Although the biochemistry of fatty acid and membrane synthesis is well-known, how membrane synthesis is balanced with growth and metabolism has remained unclear. This is partly due to the many control points that have been discovered within the membrane synthesis pathways. By precisely establishing the contributions of individual pathway enzymes, our results simplify the model of membrane biogenesis in the model bacteria species Escherichia coli. Specifically, we find that allosteric control of a single enzyme, PlsB, is sufficient to balance growth with membrane synthesis and to ensure that growing E. coli produces sufficient membrane. Identifying the signals that activate and deactivate PlsB will answer the question of how membrane synthesis is synchronized with growth.


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