Sphingolipid‐enriched domains in fungi

Santos, Filipa C.; Marquês, Joaquim T.; Bento-Oliveira, Andreia; Almeida, Rodrigo F.M. de

doi:10.1002/1873-3468.13986

Cited by 26 publications

(14 citation statements)

References 137 publications

(274 reference statements)

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“…18 This might be related to the presence of gel-like domains, enriched in sphingolipid, lacking ergosterol. 19 The relative structural and dynamic effects of cholesterol and ergosterol on lipid bilayers have been studied in detail by both experimental and computational approaches. However, these studies on binary and ternary have yielded different, if not contradictory results.…”

Section: ■ Introductionsupporting

confidence: 91%

“…It is therefore unlikely that ergosterol directly contributes to increased order of fungal PM. An alternative hypothesis for the generation of a gel-like fungal membranes has recently been put forward, where complex sphingolipids in the extracellular leaflet of the PM are responsible for the formation of tightly packed domains that are devoid of sterols . Ergosterol, which has been reported to be enriched on the cytosolic leaflet, would then rather be enriched in liquid ordered regions of the PM that intersperse with the gel domains and have no critical role in generating increased order .…”

Section: Discussionmentioning

confidence: 99%

“…Concerning the distribution of sterols, cholesterol has not shown a strong preference in the inner or outer leaflet, whereas ergosterol is concentrated mainly in the inner leaflet, equivalent to 45% of all lipids there . This might be related to the presence of gel-like domains, enriched in sphingolipid, lacking ergosterol …”

Section: Introductionmentioning

confidence: 94%

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Effect of Cholesterol Versus Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

et al. 2021

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Sterols have been ascribed a major role in the organization of biological membranes, in particular for the formation of liquid ordered domains in complex lipid mixtures. Here, we employed molecular dynamics simulations to compare the effects of cholesterol and ergosterol as the major sterol of mammalian and fungal cells, respectively, on binary mixtures with 1,2-dipalmitoyl-sn-glycero-3phosphocholine (DPPC) as a proxy for saturated lipids. In agreement with previous work, we observe that the addition of sterol molecules modifies the order of DPPC both in the gel phase and in the liquid phase. When disentangling the overall tilt angle and the structure of the tail imposed by trans/gauche configurations of torsion angles in the tail, respectively, a more detailed picture of the impact of sterols can be formulated, revealing, for example, an approximate temperature-concentration superposition ranging from the liquid to the gel phase. Furthermore, a new quantitative measure to identify the presence of collective sterol effects is discussed. Moreover, when comparing both types of sterols, addition of cholesterol has a noticeably stronger impact on phospholipid properties than that of ergosterol. The observed differences can be attributed to higher planarity of the cholesterol ring system. This planarity combined with an inherent asymmetry in its molecular interactions leads to better alignment and hence stronger interaction with saturated acyl chains. Our results suggest that the high order demonstrated for ergosterol in fungal plasma membranes must therefore be generated via additional mechanisms.

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Section: ■ Introductionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Effect of Cholesterol Versus Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

et al. 2021

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“…An alternative hypothesis for the generation of a gel-like fungal membranes has recently been put forward, where complex sphingolipids in the extracellular leaflet of the PM are responsible for the formation of tightly packed domains that are devoid of sterols. 19 Ergosterol, which has been reported to be enriched on the cytosolic leaflet, 18 would then rather be enriched in liquid ordered regions of the PM that intersperse with the gel domains and have no critical role in generating increased order. 3 It remains to be determined, whether ergosterol has stronger or weaker interactions with sphingolipid domains in the opposing leaflet.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cholesterol vs. Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

Alavizargar¹,

Keller²,

Heuer³

2020

Preprint

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Cholesterol and ergosterol are two dominant sterols in the membranes of eukaryotic and yeast cells, respectively. Although their chemical structure is very similar, their impact on the structure and dynamics of membranes differs. In this work, we have explored the effect of these two sterols on binary mixtures with 1,2-dipalnitoyl-sn-glycerol-3-phosphocholine (DPPC) lipid bilayer at various sterol concentration and temperatures, employing molecular dynamics simulations. The simulations revealed that cholesterol has a stronger impact on the ordering of the lipid chains and leads to more condensed membranes with respect to ergosterol. This difference likely arises from a more planar structure of the ring part as well as the better alignment of cholesterol among the DPPC chains with respect to ergosterol. The degree of the planarity of the ring system affects the orientation of the methyl groups on the rough side and distribute the lipid chains on the two sides of the sterols differently. Similar to the structural observations, cholesterol also has a stronger influence on the dynamics, and consistently, establishes stronger DPPC-sterol interactions when compared to ergosterol. Although our findings are consistent with some previous simulations as well as recent experiments, they are at odds with some other studies. Therefore, the presented results may shed new lights on the impact of sterols on the saturated lipids bilayers with implications for binary mixtures of lipids as well as lipid rafts.SignificanceCholesterol and ergosterol are crucial lipid molecules of eukaryotic and prokaryotic cells, respectively, with an important role for the characteristics of the membranes. Surprisingly, many experimental studies have reported opposing results concerning their relative impact. Our work aims to understand the molecular mechanism behind the influence of these sterols on the properties of saturated DPPC chains via a systematic computational approach at atomic resolution. The results show that cholesterol has a higher impact on the ordering, condensing and dynamics of the lipid chains and closely interact with them due to its more planar structure as compared to ergosterol. These effects can have implications in lipid rafts and the interaction of therapeutic drugs with membranes.

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“…The addition of glucuronic acid (GlcA) to the IPC backbone to generate GlcA-IPC, catalysed by INOSITOLPHOSPHATE CERAMIDE GLUCURONOSYLTRANSFERASE, is specific to plants ( Rennie et al , 2014 ) and these can be, and typically are, further glycosylated. In contrast, IPC, di-IPC, mannosyl-IPC, and mannosyldi-IPC are phosphosphingolipids found in fungi and yeast ( Santos et al , 2020 ). In animals, phosphosphingolipids are present as sphingomyelin bearing a phosphocholine headgroup; these are hallmark components of the myelin sheaths of nerve cell axons.…”

Section: Introductionmentioning

confidence: 99%

Diversity in sphingolipid metabolism across land plants

Haslam¹,

Feußner

2022

Journal of Experimental Botany

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Sphingolipids are essential metabolites found in all plant species. They are required for plasma membrane integrity, tolerance of and responses to biotic and abiotic stresses, and intracellular signalling. There is extensive diversity in the sphingolipid content of different plant species, and in the identities and roles of enzymes required for their processing. In this review, we survey results obtained from investigations of the classical genetic model Arabidopsis thaliana, from assorted dicots with less extensive genetic toolkits, from the model monocot Oryza sativa, and finally from the model bryophyte Physcomitrium patens. For each species or group, we first broadly summarize what is known about sphingolipid content. We then discuss the most insightful and puzzling features of modifications to the hydrophobic ceramides, and to the polar headgroups of complex sphingolipids. Altogether, this data can serve as a framework for our knowledge of sphingolipid metabolism across the plant kingdom. This chemical and metabolic heterogeneity underpins equally diverse functions. With greater availability of different tools for analytical measurements and genetic manipulation, our field is entering an exciting phase of expanding our knowledge of the biological functions of this persistently cryptic class of lipids.

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Sphingolipid‐enriched domains in fungi

Cited by 26 publications

References 137 publications

Effect of Cholesterol Versus Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

Effect of Cholesterol Versus Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

Effect of Cholesterol vs. Ergosterol on DPPC Bilayer Properties: Insights from Atomistic Simulations

Diversity in sphingolipid metabolism across land plants

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