Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity

Campomanes, Pablo; Zoni, Valeria; Vanni, Stefano

doi:10.1038/s42004-019-0175-7

Cited by 49 publications

(54 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To investigate the role of seipin in LD formation in silico, we embedded a model of the seipin 11-mer, consisting of its luminal structure and of its transmembrane (TM) helices ( Figure 1A), in lipid bilayers composed of di-oleoyl-phosphatidylcholine (DOPC) with varying concentrations of TG molecules. Our model derives from the luminal structure of human seipin recently solved using cryo-EM (28) and our models for the protein and lipids are consistent with the coarse-grain (CG) SDK/SPICA force field (38)(39)(40).…”

Section: Seipin Promotes the Accumulation Of Tg Molecules At Low Tg Csupporting

confidence: 53%

Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Zoni

Shinoda

2020

Preprint

Self Cite

View full text Add to dashboard Cite

Lipid droplets (LD) are intracellular organelles responsible for lipid storage, and they emerge from the endoplasmic reticulum (ER) upon the accumulation of neutral lipids, mostly triglycerides (TG), between the two leaflets of the ER membrane. LD biogenesis takes place at ER sites that are marked by the protein seipin, which subsequently recruits additional proteins to catalyse LD formation. Deletion of seipin, however, does not abolish LD biogenesis, and its precise role in controlling LD assembly remains unclear. Here we use molecular dynamics simulations to investigate the molecular mechanism through which seipin promotes LD formation. We find that seipin clusters TG molecules inside its unconventional ring-like oligomeric structure, and that both its luminal and transmembrane regions contribute to this process. Diacylglycerol, the precursor of TG, also clusters inside the seipin oligomer, in turn promoting TG accumulation. Our results suggest that seipin remodels the membrane of specific ER sites to prime them for LD biogenesis.

show abstract

Section: Seipin Promotes the Accumulation Of Tg Molecules At Low Tg Csupporting

confidence: 53%

Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Zoni

Shinoda

2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…DGAT1 is a membrane-bound O-acyltransferase (MBOAT) and is localized in ER (Shockey et al, 2006). Excessive DAG can induce nonlamellar phases in membrane systems (Campomanes et al, 2019;López-García et al, 1994). Recent progress has implicated DGAT1 in abiotic stress tolerance concerning cold and freezing tolerances (Arisz et al, 2018;Tan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

On the Role of DGAT1 in Seed Glycerolipid Metabolic Network and Critical Stages of Plant Development in Arabidopsis

Wang

Xia

et al. 2020

Lipids

View full text Add to dashboard Cite

Studies on the model plant Arabidopsis thaliana have uncovered the identities of most enzymatic components involved in seed storage lipid biosynthesis. However, much remains to be learned on how pathway interactions operate in the seed metabolic network. In this study, we dissected seed glycerolipid molecular compositional changes in the Arabidopsis mutant deficient in diacylglycerol acyltransferase 1 (DGAT1). Our results indicate that metabolic adjustments occurred in both phosphatidylcholine synthesis and deacylation in developing seeds. Ultrastructural changes of perturbed oil and protein bodies were also evident in cotyledon parenchyma cells. To unmask the physiological and developmental role associated with DGAT1-mediated neutral lipid biosynthesis, we attempted to combine dgat1 mutation with lpcat2 that harbors a defect in lysophosphatidylcholine acyltransferase 2 (LPCAT2). Disruption in both DGAT1 and LPCAT2 led to an apparent defect in pollen development that manifested as pollen sterility. Collectively, our results highlight a role of DGAT1 in both storage lipid synthesis and plant development.

show abstract

“…In particular, the FAE1_GPAT5 strain contained significantly higher relative amounts of conically shaped DAGs ( Figure 3B). Previously published results of membrane simulations show that high levels of DAGs are able to break the lamellar structure of the plasma membrane, reducing its integrity (28). Other research has shown that DAGs can be highly localised in specific areas of the membrane during cellular growth (29), potentially increasing the damage to the lamellar structure of the membrane.…”

Section: Storage Lipidsmentioning

confidence: 99%

Molecular-dynamics-simulation-guided membrane engineering of Saccharomyces cerevisiae by overexpression of plant FAE1 and GPAT5 genes increases fatty acid chain length in membrane lipids

Maertens

Scrima

Lambrughi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The use of lignocellulosic-based fermentation media will be a necessary part of the transition to a circular bio-economy. These media contain many inhibitors to microbial growth, including acetic acid. Under industrially relevant conditions, acetic acid enters the cell predominantly through passive diffusion across the plasma membrane. The lipid composition of the membrane determines the rate of uptake of acetic acid, and thicker, more rigid membranes impede passive diffusion. Results We hypothesized that the elongation of glycerophospholipid fatty acids would lead to thicker and more rigid membranes, reducing the influx of acetic acid. Molecular dynamics simulations were used to predict the changes in membrane properties. Overexpression of Arabidopsis thaliana genes FAE1 and GPAT5 increased the average fatty acid chain length. However, this did not lead to a reduction in the net uptake rate of acetic acid. Conclusions Despite successful strain engineering, the net uptake rate of acetic acid did not decrease. We suggest that changes in the relative abundance of certain membrane lipid headgroups could mitigate the effect of longer fatty acid chains, resulting in a higher net uptake rate of acetic acid.

show abstract

Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity

Cited by 49 publications

References 68 publications

Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

On the Role of DGAT1 in Seed Glycerolipid Metabolic Network and Critical Stages of Plant Development in Arabidopsis

Molecular-dynamics-simulation-guided membrane engineering of Saccharomyces cerevisiae by overexpression of plant FAE1 and GPAT5 genes increases fatty acid chain length in membrane lipids

Contact Info

Product

Resources

About