Functional diversity in a lipidome

Raghu, Padinjat

doi:10.1073/pnas.2004764117

Cited by 9 publications

(4 citation statements)

References 19 publications

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“…‘Why do cells possess a highly diverse lipidome?’ is one of the most perplexing questions in biology. Diversity amongst various classes of lipids arising from the variability in FA compositions such as chain length, degree of unsaturation, is turning out to be crucial for biological functions ( Atilla-Gokcumen et al, 2014 ; Khandelwal et al, 2021 ; Raghu, 2020 ; Shin et al, 2020 ). Earlier in vivo studies have pointed to the exclusive role of selective DAG subspecies in determining the fate of different physiological processes including signal transduction, cell polarity, membrane trafficking, ligand binding to membrane receptors, and modulation of membrane properties ( Lee et al, 1991 ; Marignani et al, 1996 ; Schuhmacher et al, 2020 ; Ware et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes

Mondal

Kinatukara

Singh

et al. 2022

eLife

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Chain-length specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remains unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. DIP2 is associated with vacuoles through mitochondria-vacuole contact sites and such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation.

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Section: Discussionmentioning

confidence: 99%

DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes

Mondal

Kinatukara

Singh

et al. 2022

eLife

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“…In conclusion, this study lays the necessary groundwork for further research on the pathophysiology, biomarkers discovery, and pharmacologic intervention of lipid-related diseases in parrots such as atherosclerosis and hepatic lipidosis, which are exceedingly common in captivity. Lipid biomarkers of lipid-related diseases in humans are often lipid mediators such as those derived from polyunsaturated fatty acids (arachidonic acid, ALA, DHA, EPA) as part of the microlipidome or glycerophospholipids such as PCs, PEs, and PIs or metabolite intermediates and precursors of structural lipids such as non-esterified fatty acids, ceramides, LPCs, LPC-Os, DGs, and a variety of small lipid molecules [ 20 , 22 , 41 , 49 , 62 , 63 ]. In Quaker parrots, some of the relative abundance and importance of these lipids is very similar to humans such as for most PCs and DGs while it is very different for others such as non-esterified fatty acids and ceramides.…”

Section: Discussionmentioning

confidence: 99%

The plasma lipidome of the Quaker parrot (Myiopsitta monachus)

Beaufrère¹,

Gardhouse²,

Wood³

2020

PLoS ONE

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Dyslipidemias and lipid-accumulation disorders are common in captive parrots, in particular in Quaker parrots. Currently available diagnostic tests only measure a fraction of blood lipids and have overall problematic cross-species applicability. Comprehensively analyzing lipids in the plasma of parrots is the first step to better understand their lipid metabolism in health and disease, as well as to explore new lipid biomarkers. The plasma lipidome of 12 Quaker parrots was investigated using UHPLC-MS/MS with both targeted and untargeted methods. Targeted methods on 6 replicates measured 432 lipids comprised of sterol, cholesterol ester, bile acid, fatty acid, acylcarnitine, glycerolipid, glycerophospholipid, and sphingolipid panels. For untargeted lipidomics, precursor ion mass-to-charge ratios were matched to corresponding lipids using the LIPIDMAPS structure database and LipidBlast at the sum composition or acyl species level of information. Sterol lipids and glycerophospholipids constituted the majority of plasma lipids on a molar basis. The most common lipids detected with the targeted methods included free cholesterol, CE(18:2), CE(20:4) for sterol lipids; PC(36:2), PC(34:2), PC(34:1) for glycerophospholipids; TG(52:3), TG(54:4), TG(54:5), TG(52:2) for glycerolipids; SM(d18:1/16:0) for sphingolipids; and palmitic acid for fatty acyls. Over a thousand different lipid species were detected by untargeted lipidomics. Sex differences in the plasma lipidome were observed using heatmaps, principal component analysis, and discriminant analysis. This report presents the first comprehensive database of plasma lipid species in psittacine birds and paves the way for further research into blood lipid diagnostics and the impact of diet, diseases, and drugs on the parrot plasma lipidome.

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“…Lipids are complex biomolecules, consisting of a head group that is esterified to hydrophobic tails, produced by cells by means of enzyme action from simpler components 33 . Lipids are an essential constituent of both cell membranes and lipid‐based particles, including extracellular vesicles and lipoproteins 34,35 .…”

Section: Lipidomicsmentioning

confidence: 99%

Science‐in‐brief: Proteomics and metabolomics in equine veterinary science

Anderson

2022

Equine Veterinary Journal

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Functional diversity in a lipidome

Cited by 9 publications

References 19 publications

DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes

DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes

The plasma lipidome of the Quaker parrot (Myiopsitta monachus)

Science‐in‐brief: Proteomics and metabolomics in equine veterinary science

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