Recent advances in expanding the coverage of the lipidome

Tumanov, Sergey; Kamphorst, Jurre J.

doi:10.1016/j.copbio.2016.11.008

Cited by 63 publications

(37 citation statements)

References 55 publications

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“…The challenges of studying lipidomic rather than genetic or proteomic factors of disease have been discussed in detail 87 , yet the results we present here in human cells and by others in the flavivirus arthropod vector 88–90 argue strongly for the equal importance of lipids in questions of ZIKV pathogenesis. Our evidence that sphinganine and sphingosine are strongly linked to diseases with phenotypes that are clinically similar to ZIKV syndrome further implicates the sphingolipid network as contributing to the molecular processes underlying ZIKV virulence.…”

Section: Discussionmentioning

confidence: 73%

A global lipid map defines a network essential for Zika virus replication

Leier

Weinstein

Kyle

et al. 2020

Preprint

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26Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form 27 replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for 28 disease, is poorly understood. Here, we performed comprehensive lipidomics to create a lipid 29 network map during ZIKV infection. We found that ZIKV significantly alters host lipid 30 composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic 31 expression of ZIKV NS4B protein resulted in similar changes, demonstrating a role for NS4B in 32 modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, 33including human neural progenitor cells, blocked ZIKV infection. Additionally, the sphingolipid 34 ceramide redistributes to ZIKV replication sites and increasing ceramide levels by multiple 35 pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network 36 with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV 37 infection. Results 112 ZIKV alters the lipid landscape of host cells 113To understand how cellular lipid metabolism is altered by ZIKV infection, we carried out 114 a global lipidomic survey of the model Huh7 human hepatic carcinoma cell line 20 infected for 24 115 or 48 hours with Asian lineage ZIKV strain FSS13025 (Fig. 1a). Lipids extracted from 116 populations of mock and infected cells (n = 5 biological replicates per condition) were analyzed 117 with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Supplementary Data 118 1 and Supplementary Fig. 1a-f). We identified 340 lipid species spanning the phospholipid, 119 sphingolipid, glycerolipid, and sterol classes for which pairwise comparisons of normalized 120 abundance between mock and infected cells could be made (Supplementary Data 1). Of these, 121 80 species (23.5%) showed significant changes in abundance by 24 hours post-infection (hpi) 122 and 172 species (50.6%) were significantly altered by 48 hpi (P < 0.05, ANOVA or g-test) 123( Supplementary Data 1). Principal component analysis (PCA) of these observations confirmed 124 that infection status (mock or ZIKV) and timepoint (24 or 48 hpi) accounted most of these 125 changes, with changes in lipid composition between mock and infected cells increasing over 126 time (Fig. 1b). 127Next, we examined how ZIKV-induced changes in host lipid composition broke down by 128 subclass and species (Fig. 1c, d). A map of the pairwise correlations of all 340 species at 48 hpi 129 ( Supplementary Fig. 2a) revealed that lipid subclasses largely fell into two groups of species 130 that were either enriched or depleted in abundance ( Supplementary Fig. 2b), suggesting that 131 individual metabolic pathways are up-or down-regulated to create a specific lipid milieu around 132 the events of the viral replication cycle. Supporting this, many of the trends we observed were 133 consistent with earlier reports of functional roles for lipids during flavivirus infection. In ...

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Section: Discussionmentioning

confidence: 73%

A global lipid map defines a network essential for Zika virus replication

Leier

Weinstein

Kyle

et al. 2020

Preprint

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“…NPLC and RPLC both provide high quality lipid separations and even 2D LC separations can be obtained by collecting the normal phase fractions for reversed phase analyses, or vice versa, to acquire better resolution for isolation of lipid species. More recently, hydrophilic interaction liquid chromatography (HILIC) has even been utilized to separate lipids and it has shown promising results for lysophospholipid regioisomers [13,14]. All of these LC techniques have been used for qualitative and quantitative lipid analysis, providing important information about complex samples [15–17].…”

Section: Mass Spectrometry-based Lipid Measurementsmentioning

confidence: 99%

Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches

Zheng

Smith

Baker

2018

Current Opinion in Chemical Biology

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Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have greatly progressed knowledge about distinct lipid species and functions, effectively separating many lipids still remains problematic. Isomeric lipids have made lipid characterization especially difficult and occur due to subclasses having the same chemical composition, or species having multiple acyl chain connectivities (sn-1, sn-2, or sn-3), double bond positions and orientations (cis or trans), and functional group stereochemistries (R versus S). To aid in isomer characterization, ion mobility spectrometry separations, ion-molecule reactions and fragmentation techniques have increasingly been added to lipid analysis workflows. In this manuscript, we review the current state of these approaches and their capabilities for improving the identification of lipid species.

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“…The ability to maintain specific membrane compartments with distinct protein and lipid compositions directly facilitates the spatial organization of metabolic functions that underlie cellular homeostasis. Our current understanding of membrane composition has benefitted greatly from biomolecular separation techniques such as high-performance thin-layer chromatography, as well as, more recently, though the establishment of comprehensive lipidomics methodologies (Shevchenko and Simons, 2010; Wenk, 2010; Harkewicz and Dennis 2011; Tumanov and Kamphorst, 2017). However, these approaches lack spatial information related to how lipid species are distributed or transported throughout the membrane compartments that exist within an intact cell.…”

Section: Introductionmentioning

confidence: 99%

Defining the Subcellular Distribution and Metabolic Channeling of Phosphatidylinositol

Pemberton

Kim

Sengupta

et al. 2019

Preprint

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1 Pemberton et al. characterize a molecular toolbox for the visualization and manipulation of 2 phosphatidylinositol (PtdIns) within intact cells. Results using these approaches define the steady-state 3 distribution of PtdIns across subcellular membrane compartments as well as provide new insights into the 4 relationship between PtdIns availability and polyphosphoinositide turnover. 5 6 7 Abstract 8Phosphatidylinositol (PtdIns) is an essential structural component of eukaryotic membranes that also 9 serves as the common precursor for polyphosphoinositide (PPIn) lipids. Despite the recognized importance 10 of PPIn species for signal transduction and membrane homeostasis, there is still a limited understanding of 11 how the dynamic regulation of PtdIns synthesis and transport contributes to the turnover of PPIn pools. To 12 address these shortcomings, we capitalized on the substrate selectivity of a bacterial enzyme, PtdIns-specific 13 PLC, to establish a molecular toolbox for investigations of PtdIns distribution and availability within intact cells. 14 In addition to its presence within the ER, our results reveal low steady-state levels of PtdIns within the plasma 15 membrane (PM) and endosomes as well as a relative enrichment of PtdIns within the cytosolic leaflets of the 16 Golgi complex, peroxisomes, and outer mitochondrial membranes. Kinetic studies also demonstrate the 17 requirement for sustained PtdIns supply from the ER for the maintenance of monophosphorylated PPIn 18 species within the PM, Golgi complex, and endosomal compartments. 19

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Recent advances in expanding the coverage of the lipidome

Abstract: Graphical abstract

Cited by 63 publications

References 55 publications

A global lipid map defines a network essential for Zika virus replication

A global lipid map defines a network essential for Zika virus replication

Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches

Defining the Subcellular Distribution and Metabolic Channeling of Phosphatidylinositol

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