Tracing Lipid Metabolism by Alkyne Lipids and Mass Spectrometry: The State of the Art

Kuerschner, Lars; Thiele, Christoph

doi:10.3389/fmolb.2022.880559

Cited by 7 publications

(5 citation statements)

References 71 publications

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“…A comprehensive understanding of FAs metabolism in bacteria, including metabolite flow and kinetics is lacking, even more so in cyanobacteria. To this aim, isotopic labeling is the most widely used method to trace lipid metabolism by mass spectrometry lipidomics; however, recent development of non-invasive methods based on click and bioorthogonal chemistry, such as azides reporters, alkyne lipids and analogs, lipid head group labeling as well as their detection procedures, are opening new avenues both for tracing lipid metabolism by mass spectrometry lipidomics as well as tracking their localization by optical and electron microscopy (Gerbersdorf 2006 , Kurmayer et al 2020 , Morón-Asensio et al 2021 , Kuerschner and Thiele 2022 ). Such new methodologies have led to considerable progress in understanding the evolution and development of early life forms (Bhattacharya et al 2019 ).…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Incorporation, fate, and turnover of free fatty acids in cyanobacteria

Kahn

Oliveira

Cuau

et al. 2023

FEMS Microbiology Reviews

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Fatty acids are important molecules in bioenergetics and also in industry. The phylum Cyanobacteria consists of a group of prokaryotes that typically carry out oxygenic photosynthesis with water as an electron donor and use carbon dioxide as a carbon source to generate a range of biomolecules, including fatty acids. They are also able to import exogenous free fatty acids and direct them to biosynthetic pathways. Here, we review current knowledge on mechanisms and regulation of free fatty acid transport into cyanobacterial cells, their subsequent activation and use in the synthesis of fatty acid-containing biomolecules such as glycolipids and alka(e)nes, as well as recycling of free fatty acids derived from such molecules. This review also covers efforts in the engineering of such cyanobacterial fatty acid-associated pathways en route to optimized biofuel production.

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Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Incorporation, fate, and turnover of free fatty acids in cyanobacteria

Kahn

Oliveira

Cuau

et al. 2023

FEMS Microbiology Reviews

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“…Bez mutants accumulate lipids of both types, the neutral lipids (DG, TG) and phospholipids (PE, PC, Supplemental Figure 6E). To investigate how Bez affects uptake and incorporation of fatty acids into the lipidome of the fat body we incubated isolated tissue of control flies and Bez mutants with alkyne-labeled oleic acid (alkyne oleate, FA 19:1;Y) a traceable analog of the abundant natural oleic acid (Kuerschner & Thiele, 2022). Upon click-reaction a mass spectrometry lipidome analysis was performed (Wunderling et al, 2021).…”

Section: Bez Loss-of-function Alters Lipid Droplet Size and Lipid Upt...mentioning

confidence: 99%

The CD36 scavenger receptor Bez regulates lipid redistribution from fat body to oocytes in Drosophila

Carrera,

Odenthal,

Risse

et al. 2023

Preprint

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Class B scavenger receptors of the CD36 family are important for lipid mobilization from mammalian adipose tissue. This protein family has 3 members in mammals, but 14 inDrosophila melanogaster. Lipid distribution inDrosophilais mediated by homologs of the LDL receptors, while little is known about the function of scavenger receptors for this process in invertebrates. Here we unravel a role for the so far uncharacterized scavenger receptor Bez in lipid export fromDrosophilaadipocytes. Bez shares the lipid binding residue with CD36 and is expressed at the plasma membrane of the embryonic, larval and adult fat body. Bez loss-of-function lowers the organismal content of storage lipids while they accumulate in the fat body, concomitant with female sterility and degeneration of ovaries. Using an alkyne-labeled fatty acid tracer, we demonstrate that Bez interacts with the apoB homolog Lipophorin at the plasma membrane of adipocytes, thereby enabling lipid transfer. Our study shows how a scavenger receptor interacts with lipoproteins to distribute storage lipids from the fat body to the ovaries and thereby contributes to the metabolic control of development.

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“…A variety of alkyne lipids have been employed as probes to study the metabolism of their endogenous counterparts, which are distinguished from the alkyne probe by MS-based methods. 50 Alternatively, through ligation to a biotin, alkyne lipids that are incorporated into proteins can be enriched to elucidate the lipidation PTM pattern using proteomics. Alkyne moieties are also incorporated in photoaffinity probes, to identify the biomolecular interaction landscape of signaling lipids.…”

Section: Lipid Reporter Functionalitiesmentioning

confidence: 99%

“…The previously mentioned alkyne moiety is a popular tag for omega-terminal fatty acid chain functionalization, due to its similarity in size and hydrophobicity with respect to the substituted alkyl group. A variety of alkyne lipids have been employed as probes to study the metabolism of their endogenous counterparts, which are distinguished from the alkyne probe by MS-based methods . Alternatively, through ligation to a biotin, alkyne lipids that are incorporated into proteins can be enriched to elucidate the lipidation PTM pattern using proteomics.…”

Section: Visualizing and Controlling Lipid Transfer And Actionmentioning

confidence: 99%

Chemical Probes to Control and Visualize Lipid Metabolism in the Brain

2022

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Conspectus Signaling lipids, such as the endocannabinoids, play an important role in the brain. They regulate synaptic transmission and control various neurophysiological processes, including pain sensation, appetite, memory formation, stress, and anxiety. Unlike classical neurotransmitters, lipid messengers are produced on demand and degraded by metabolic enzymes to control their lifespan and signaling actions. Chemical biology approaches have become one of the main driving forces to study and unravel the physiological role of lipid messengers in the brain. Here, we review how the development and use of chemical probes has allowed one to study endocannabinoid signaling by (i) inhibiting the biosynthetic and metabolic enzymes; (ii) visualizing the activity of these enzymes; and (iii) controlling the release and transport of the endocannabinoids. Activity-based probes were instrumental to guide the discovery of highly selective and in vivo active inhibitors of the biosynthetic (DAGL, NAPE-PLD) and metabolic (MAGL, FAAH) enzymes of endocannabinoids. These inhibitors allowed one to study the role of these enzymes in animal models of disease. For instance, the DAGL–MAGL axis was shown to control neuroinflammation and the NAPE-PLD–FAAH axis to regulate emotional behavior. Activity-based protein profiling and chemical proteomics were essential to guide the drug discovery and development of compounds targeting MAGL and FAAH, such as ABX-1431 (Lu AG06466) and PF-04457845, respectively. These experimental drugs are now in clinical trials for multiple indications, including multiple sclerosis and post-traumatic stress disorders. Activity-based probes have also been used to visualize the activity of these lipid metabolizing enzymes with high spatial resolution in brain slices, thereby showing the cell type-specific activity of these lipid metabolizing enzymes. The transport, release, and uptake of signaling lipids themselves cannot, however, be captured by activity-based probes in a spatiotemporal controlled manner. Therefore, bio-orthogonal lipids equipped with photoreactive, photoswitchable groups or photocages have been developed. These chemical probes were employed to investigate the protein interaction partners of the endocannabinoids, such as putative membrane transporters, as well as to study the functional cellular responses within milliseconds upon irradiation. Finally, genetically encoded sensors have recently been developed to monitor the real-time release of endocannabinoids with high spatiotemporal resolution in cultured neurons, acute brain slices, and in vivo mouse models. It is anticipated that the combination of chemical probes, highly selective inhibitors, and sensors with advanced (super resolution) imaging modalities, such as PharmacoSTORM and correlative light-electron microscopy, will uncover the fundamental basis of lipid signaling at nanoscale resolution in the brain. Furthermore, chemical biology approaches enable the translation of these fundamental discoveries into clinical solutions for brain dis...

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Tracing Lipid Metabolism by Alkyne Lipids and Mass Spectrometry: The State of the Art

Cited by 7 publications

References 71 publications

Incorporation, fate, and turnover of free fatty acids in cyanobacteria

Incorporation, fate, and turnover of free fatty acids in cyanobacteria

The CD36 scavenger receptor Bez regulates lipid redistribution from fat body to oocytes in Drosophila

Chemical Probes to Control and Visualize Lipid Metabolism in the Brain

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