Faculty Opinions recommendation of Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism.

2010 ◽  
Author(s):  
Linda Huang
Keyword(s):  
Phosphatidic Acid ◽  
Membrane Biogenesis

scholarly journals Toxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sheena Dass ◽  
Serena Shunmugam ◽  
Laurence Berry ◽  
Christophe-Sebastien Arnold ◽  
Nicholas J. Katris ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Phosphatidic Acid ◽  
De Novo ◽  
Lipid Synthesis ◽  
Parasite Development ◽  
Membrane Biogenesis ◽  
Membrane Phospholipids ◽  
Phosphatidic Acid Phosphatase ◽  
Intracellular Parasites ◽  
Parasite Survival

AbstractApicomplexa are obligate intracellular parasites responsible for major human diseases. Their intracellular survival relies on intense lipid synthesis, which fuels membrane biogenesis. Parasite lipids are generated as an essential combination of fatty acids scavenged from the host and de novo synthesized within the parasite apicoplast. The molecular and metabolic mechanisms allowing regulation and channeling of these fatty acid fluxes for intracellular parasite survival are currently unknown. Here, we identify an essential phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as the central metabolic nexus responsible for controlled lipid synthesis sustaining parasite development. Lipidomics reveal that TgLIPIN controls the synthesis of diacylglycerol and levels of phosphatidic acid that regulates the fine balance of lipids between storage and membrane biogenesis. Using fluxomic approaches, we uncover the first parasite host-scavenged lipidome and show that TgLIPIN prevents parasite death by ‘lipotoxicity’ through effective channeling of host-scavenged fatty acids to storage triacylglycerols and membrane phospholipids.

scholarly journals The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1

2018 ◽  
Vol 217 (9) ◽  
pp. 3109-3126 ◽  
Author(s):  
Harald F. Hofbauer ◽  
Michael Gecht ◽  
Sabine C. Fischer ◽  
Anja Seybert ◽  
Achilleas S. Frangakis ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Rational Design ◽  
Acyl Chain ◽  
Membrane Biogenesis ◽  
Amphipathic Helix ◽  
New Feature ◽  
Dynamics Simulations ◽  
Membrane Recognition ◽  
And Control

A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.

Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism

Science ◽  
2010 ◽  
Vol 329 (5995) ◽  
pp. 1085-1088 ◽  
Author(s):  
B. P. Young ◽  
J. J. H. Shin ◽  
R. Orij ◽  
J. T. Chao ◽  
S. C. Li ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Membrane Biogenesis

scholarly journals The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1

2018 ◽  
Author(s):  
Harald F. Hofbauer ◽  
Michael Gecht ◽  
Sabine C. Fischer ◽  
Anja Seybert ◽  
Achilleas S. Frangakis ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Acyl Chain ◽  
Md Simulations ◽  
Membrane Biogenesis ◽  
Hydrophobic Core ◽  
Amphipathic Helix ◽  
The Family ◽  
Chain Composition ◽  
New Feature ◽  
Membrane Recognition

AbstractA key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.

Interaction of Vasopressin with Human Blood Platelets: Dependency on Mg2+

1986 ◽  
Vol 56 (03) ◽  
pp. 260-262 ◽  
Author(s):  
Isabella Roos ◽  
Fabrizia Ferracin ◽  
Alfred Pletscher
Keyword(s):  
Phosphatidic Acid ◽  
Human Blood ◽  
Arginine Vasopressin ◽  
Specific Binding ◽  
Blood Platelets ◽  
Bivalent Cations ◽  
Platelet Membranes ◽  
Maximal Rise ◽  
Human Blood Platelets ◽  
Stimulation Of

SummaryArginine-vasopressin (AVP) in the presence of Mg2+ but not in the absence of bivalent cations led to accumulation of [32P]-phosphatidic acid ([32P]-PA) in human blood platelets. Mg2+ also enhanced the specific binding of [3H]-AVP to intact platelets. The concentrations of the cation which enabled AVP to cause half maximal rise of [32P]-PA and those inducing half maximal [3H]-AVP-binding were of the same order. It is concluded that the stimulation of phosphatidyl inositide breakdown by AVP in presence of Mg2+ is at least partially due to a Mg2+-induced enhancement of specific AVP-binding to the platelet membranes.

Enhancement of the Release Reaction Not Accompanied with Enhanced Phosphatidylinositol Turnover in the Reserpinized Rabbit Blood Platelets

1983 ◽  
Vol 50 (02) ◽  
pp. 595-600 ◽  
Author(s):  
Y Watanabe ◽  
M Soda ◽  
N Fukamachi ◽  
B Kobayashi
Keyword(s):  
Phosphatidic Acid ◽  
Blood Platelets ◽  
Specific Protein ◽  
The Other ◽  
Release Reaction ◽  
Rabbit Blood ◽  
Phosphatidylinositol Turnover ◽  
Activated State ◽  
32P Incorporation ◽  
Platelet Release

SummaryThrombin-induced platelet release reaction examined with secretion of calcium and N-acetylglucosaminidase was significantly enhanced in the platelets from reserpine-treated rabbits as compared with the control. On the other hand, 32P-incorporation into phosphatidic acid was suppressed in the reserpinized platelets in activated state. Thrombin induced phosphatidylinositol (PI)- breakdown, which was examined by decreases in radioactivity and content of PI, and an increase in diacylglycerol, was not enhanced in the reserpinized platelets as compared with the control. The phosphorylation of the specific protein coupled to thrombin- induced platelet PI-breakdown was not stimulated in the reserpinized platelets as compared with the control. In contrast to PI, PC-degradation by thrombin was significantly stimulated in the reserpinized platelets. Possible existence of pathway(s) other than that associated with an enhancement of Pl-tumover is conceivable as a mechanism involved in platelet release reaction.

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