Lipidology and lipidomics––quo vadis? A new era for the physical chemistry of lipids

Mouritsen, Ole G.

doi:10.1039/c1cp22484k

Cited by 40 publications

(29 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The biophysical properties of a membrane not only regulate the activity of proteins embedded in it, as reviewed in [5], but also the recruitment and activity of peripheral, amphitropic membrane proteins that bind weakly and reversibly to membrane lipids and are only temporarily associated to the membrane. The membrane recruitment of amphitropic proteins is mediated via various hydrophobic anchor structures, such as lipid binding pockets, amphipathic helices, hydrophobic loops, or post-translationally lipidated amino acid residues [6].…”

Section: Introductionmentioning

confidence: 99%

The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and retrograde transport

et al. 2016

View full text Add to dashboard Cite

2-hydroxyoleic acid (OHOA, Minerval®) is an example of a substance used for membrane lipid therapy, where the cellular membranes rather than specific proteins constitute the therapeutical target. OHOA is thought to mediate its anti-tumor effect by affecting the biophysical properties of membranes, which leads to altered recruitment and activation of amphitropic proteins, altered cellular signaling, and eventual cell death. Little is known about the initial signaling events upon treatment with OHOA, and whether the altered membrane properties would have any impact on the dynamic intracellular transport system. In the present study we demonstrate that treatment with OHOA led to a rapid release of intracellular calcium and activation of multiple signaling pathways in HeLa cells, including the PI3K-AKT1-MTOR pathway and several MAP kinases, in a process independent of the EGFR. By lipidomics we confirmed that OHOA was incorporated into several lipid classes. Concomitantly, OHOA potently increased retrograde transport of the plant toxin ricin from endosomes to the Golgi and further to the endoplasmic reticulum. The OHOA-stimulated ricin transport seemed to require several amphitropic proteins, including Src, phospholipase C, protein kinase C, and also Ca2+/calmodulin. Interestingly, OHOA induced a slight increase in endosomal localization of the retromer component VPS35. Thus, our data show that addition of a lipid known to alter membrane properties not only affects signaling, but also intracellular transport.

show abstract

Section: Introductionmentioning

confidence: 99%

The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and retrograde transport

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For example, the membrane proteins are well known the form channels, pumps, and receptors, that all often contain a few monomers. 26 Another interesting example, related potentially to Alzheimer's disease, is aggregation of amyloid β-peptides on the membrane of neurons. 41,42 Many other examples can be found.…”

Section: Resultsmentioning

confidence: 99%

“…Expression (25) implies that the monomer binding energy, ∆E i , is constant, while according to expression (26) this energy decreases with increasing i as ∼ 1/(i − 1) 1/2 . These two dependences of ∆E i on i are physically reasonable.…”

Section: Specification Of the Detailsmentioning

confidence: 99%

“…contain a few proteins or peptides while large aggregates may be mesoscopic as in the case of lipid domains which can be formed in membranes composed of different lipids. [24][25][26][27][28] Physically, the size and structure of aggregates depend on the type of particle-particle lateral interactions (see, e.g. simulations [29][30][31][32] ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Kinetics of Single-Enzyme Reactions on Vesicles: Role of Substrate Aggregation

Zhdanov

2015

Biophys. Rev. Lett.

View full text Add to dashboard Cite

Enzymatic reactions occurring in vivo on lipid membranes can be influenced by various factors including macromolecular crowding in general and substrate aggregation in particular. In academic studies, the role of these factors can experimentally be clarified by tracking single-enzyme kinetics occurring on individual lipid vesicles. To extend the conceptual basis for such experiments, we analyze herein the corresponding kinetics mathematically with emphasis on the role of substrate aggregation. In general, the aggregation may occur on different length scales. Small aggregates may e.g. contain a few proteins or peptides while large aggregates may be mesoscopic as in the case of lipid domains which can be formed in the membranes composed of different lipids. We present a kinetic model describing comprehensively the effect of aggregation of the former type on the dependence of the reaction rate on substrate membrane concentration. The results obtained with physically reasonable parameters indicate that the aggregationrelated deviations from the conventional Michaelis-Menten kinetics may be appreciable. Special Issue Comments:This theoretical article is focused on single-enzyme reactions occurring in parallel with substrate aggregation on individual vesicles. This subject is related to a few Special Issue articles concerning enzyme dynamics 6,7 and function 8 and mathematical aspects of stochastic kinetics. 9

show abstract

“…It is well known that more than 25% of proteins bind to cell membranes and their function is highly dependent on the membrane–protein interactions [1,2,3]. Thus, constructing model membranes with less complicated lipid mixtures or individual lipids is very important to gain information on the binding of proteins to membranes [4,5]. Phospholipid monolayers are the most important and popular model among the various model membrane systems developed.…”

Section: Introductionmentioning

confidence: 99%

Effect of N- and C-Terminal Amino Acids on the Interfacial Binding Properties of Phospholipase D from Vibrio parahaemolyticus

Wang

Wei

Abousalham

et al. 2018

IJMS

View full text Add to dashboard Cite

The effects of N-terminal (1–34 amino acids) and C-terminal (434–487 amino acids) amino acid sequences on the interfacial binding properties of Phospholipase D from Vibrio parahaemolyticus (VpPLD) were characterized by using monomolecular film technology. Online tools allowed the prediction of the secondary structure of the target N- and C-terminal VpPLD sequences. Various truncated forms of VpPLD with different N- or C-terminal deletions were designed, based on their secondary structure, and their membrane binding properties were examined. The analysis of the maximum insertion pressure (MIP) and synergy factor “a” indicated that the loop structure (1–25 amino acids) in the N-terminal segment of VpPLD had a positive effect on the binding of VpPLD to phospholipid monolayers, especially to 1,2-dimyristoyl-sn-glycero-3-phosphoserine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine. The deletion affecting the N-terminus loop structure caused a significant decrease of the MIP and synergy factor a of the protein for these phospholipid monolayers. Conversely, the deletion of the helix structure (26–34 amino acids) basically had no influence on the binding of VpPLD to phospholipid monolayers. The deletion of the C-terminal amino acids 434–487 did not significantly change the binding selectivity of VpPLD for the various phospholipid monolayer tested here. However, a significant increase of the MIP value for all the phospholipid monolayers strongly indicated that the three-strand segment (434–469 amino acids) had a great negative effect on the interfacial binding to these phospholipid monolayers. The deletion of this peptide caused a significantly greater insertion of the protein into the phospholipid monolayers examined. The present study provides detailed information on the effect of the N- and C-terminal segments of VpPLD on the interfacial binding properties of the enzyme and improves our understanding of the interactions between this enzyme and cell membranes.

show abstract

Lipidology and lipidomics––quo vadis? A new era for the physical chemistry of lipids

Cited by 40 publications

References 110 publications

The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and retrograde transport

The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and retrograde transport

Kinetics of Single-Enzyme Reactions on Vesicles: Role of Substrate Aggregation

Effect of N- and C-Terminal Amino Acids on the Interfacial Binding Properties of Phospholipase D from Vibrio parahaemolyticus

Contact Info

Product

Resources

About