Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional multi-organelle units control inflammatory lipid metabolism of macrophages

ABSTRACT: Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated, when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multispectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (M-ER-LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (M-ER-P-LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid synthesis. Together, we show that macrophages form functional multi-organellar units (MOUs) to support metabolic adaptation, and provide an experimental strategy to identify organelle-metabolic signaling hubs.

ORGANISM(S): Mus musculus

PROVIDER: GSE235484 | GEO | 2024/05/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of molecular machinery mediating ER to lipid droplet protein targeting

Project description:Lipid droplets (LDs) are organelles that store lipids and contain important metabolic proteins at their surfaces. The pathway for membrane-embedded hydrophobic proteins to reach the LD surface from the ER is largely unknown. Here, we find that many proteins, including key lipid synthesis and degradation enzymes, are excluded from forming LDs in the ER by the seipin oligomeric complex and target LDs via ER-LD membrane continuities that are established well after LD formation. We utilized systematic, unbiased approaches to identify key components of this ER-to-LD (ERTOLD) pathway. We find that specific membrane-fusion machinery, including membrane fusion regulators (Trs20 and Rab1), a tether (Rint1), and effectors (Syx5, membrin, Bet1, Ykt6), are required for late ERTOLD targeting of GPAT4 and other proteins that utilize this pathway. The fusion machinery components localize to the interface of LDs and the ER, and within the ER, appear to be organized at ER exit sites. Our data therefore uncover a novel mechanism for membrane protein trafficking for ERTOLD targeting via heterotypic organelle fusion between the ER and LDs.

2022-06-27 | PXD027283 | Pride

Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

Project description:Neural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.

2021-11-10 | GSE187470 | GEO

Lipid droplets protect human β-cells from lipotoxic-induced stress and cell identity changes

Project description:Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β cell function, the levels of a key LD scaffold protein, perilipin2 (PLIN2), were manipulated by lentiviral-mediated knock-down (KD) or over-expression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties. Glucose stimulated insulin secretion was blunted in PLIN2KD cells and improved in PLIN2OE cells. An unbiased transcriptomic analysis revealed that limiting LD formation induced effectors of endoplasmic reticulum (ER) stress that compromised the expression of critical β cell function and identity genes. These changes were essentially reversed by PLIN2OE or using the ER stress inhibitor, tauroursodeoxycholic acid. These results strongly suggest that LDs are essential for adult human islet β cell activity by preserving FFA homeostasis.

2021-09-15 | GSE184016 | GEO

Rab18 is not necessary for lipid droplet biogenesis or turnover in human mammary carcinoma cells

Project description:Rab GTPases recruit peripheral membrane proteins and can define organelle identity. Rab18 localizes to the ER but also to the surfaces of lipid droplets (LDs), where it has been implicated in effector protein recruitment and in defining LD identity. Here, we studied Rab18 localization and function in SUM159 cells. Rab18 localized to the ER and to LD membranes upon LD induction, with the latter depending on the Rab18 activation state. In cells lacking Rab18, LDs were modestly reduced in size and numbers, but we found little evidence for Rab18 function in LD formation, LD turnover upon cell starvation, or the targeting of several proteins to LDs. We conclude that Rab18 is not a general, necessary component of the protein machinery involved in LD biogenesis or turnover, but instead likely plays a specialized role in specific cell types

2018-06-06 | PXD009683 | Pride

Identification of a lipid droplet-plasma membrane tethering complex

Project description:Membrane contact sites (MCS) are interorganellar contacts that allow for the direct exchange of molecules such as lipids or Ca2+ between organelles, but can also be a mean for tethering of organelles. In mammals and yeast, LDs have been shown to engage in MCS with nearly all organelles in the cell, while in plants only LD-ER and LD-peroxisome contacts have been characterised. We here analyse three proteins, LD-localised SEED LIPID DROPLET PROTEIN (SLDP) 1 and 2 and PM-localised LIPID DROPLET PLASMA MEMBRANE ADAPTOR. Knockout of SLDP1 and 2, as well as knockout of LIPA lead to aberrant clustering of LDs in seedlings, while ectopic co-expression of SLDP and LIPA in Nicotiana tabacum pollen tubes is sufficient to reconstitute LD-PM tethering in this tissue, where LDs normally dynamically float in the cytosol stream. We propose a model, in which SLDP and LIPA interact and thereby form a tether to anchor a subset of LDs to the PM during post-germinative growth in Arabidopsis thaliana.

2022-06-09 | PXD022769 | Pride

Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Project description:Organelle interactions play a significant role in compartmentalizing metabolism and signaling. Lipid droplets (LDs) interact with numerous organelles including mitochondria, which is largely assumed to facilitate lipid transfer and catabolism. However, quantitative proteomics of hepatic peridroplet (PDM) and cytosolic mitochondria (CM) revealed that CM are enriched in proteins comprising various oxidative metabolism pathways whereas PDM are enriched in proteins involved in lipid anabolism. Isotope tracing and super-resolution imaging confirmed that fatty acids (FAs) are selectively trafficked to and oxidized in CM during fasting. In contrast, PDM facilitate FA esterification and LD expansion in nutrient-replete media. Additionally, mitochondrial-associated membranes (MAMs) around PDM and CM differed in their proteomes and ability to support distinct lipid metabolic pathways. We conclude that CM and CM-MAM support lipid catabolic pathways whereas PDM and PDM-MAM allow hepatocytes to efficiently store excess lipids in LDs to prevent lipotoxicity in contrast to existing dogma.

2023-03-28 | MSV000091575 | MassIVE

Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism MAM Dataset

2023-03-28 | MSV000091576 | MassIVE

A fluorescent perilipin 2 knock-in mouse model reveals a high abundance of lipid droplets in the developing and adult brain

Project description:Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by endogenously labelling the LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are highly abundant in various cell types in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we also show that LDs are abundant during brain development and can be visualized using live-imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2.

2024-05-15 | GSE267069 | GEO

Proteomics identifies organelle specific phosphorylation and reveals major subcellular reorganization in the progression of NAFLD

Project description:Obesity induced non-alcoholic fatty liver disease (NAFLD) is associated with the development of type 2 diabetes and constitutes a major health problem. A hallmark of the diseases is extensive lipid droplet (LD) formation and accumulation of toxic lipid species interfering with cellular signaling and functions. However, the cellular mechanisms during disease progression and cellular lipid overflow are poorly understood. Here, we develop a novel workflow for label free mass spectrometry based protein and phosphopeptide correlation profiling to systematically monitor the level and cellular distribution of ~6000 liver proteins and ~16,000 phosphosites during the development of dietary induced steatosis in mice. We see a redistribution of the secretory apparatus including a mislocalization of the COPI complex, and targeting of all analyzed Golgi apparatus proteins to LDs what leads to a general reduction of hepatic protein secretion. Further, we identify targeting of several organelle contact site proteins to LDs, accompanied by increased contacts between LDs and other organelles. Our resource provides the first systematic in vivo analysis of subcellular re-arrangements and organelle specific phosphorylation during disease development.

2018-10-29 | PXD007653 | Pride

The large GTPase Sey1/atlastin mediates lipid droplet- and FadL-dependent intracellular fatty acid metabolism of Legionella pneumophila

Project description:The facultative intracellular bacterium Legionella pneumophila employs the Icm/Dot type IV secretion system (T4SS) to replicate in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV). The ER-resident large fusion GTPase Sey1/atlastin-3 promotes remodeling and expansion of LCVs, and the GTPase is also implicated in the formation of ER-derived lipid droplets (LDs). Here we reveal that LCVs intimately interact with palmitate-induced LDs in Dictyostelium discoideum amoeba. Comparative proteomics of LDs isolated from the D. discoideum parental strain Ax3 or sey1 revealed 192 differentially produced proteins, of which 7 or 22 were exclusively detected in LDs isolated from strain Ax3 or sey1, respectively. Using dually fluorescence-labeled amoeba producing the LCV marker P4C-GFP or AmtA-GFP and the LD marker mCherry-perilipin, we show that Sey1 and the L. pneumophila Icm/Dot T4SS as well as the effector LegG1 promote LCV-LD interactions. In vitro reconstitution of the LCV-LD interactions using purified LCVs and LDs from D. discoideum Ax3 or sey1 revealed that Sey1 and GTP promote this process. The LCV-LD interactions were impaired forsey1-derived LDs, suggesting that Sey1 regulates LD traits. Palmitate promoted the growth of L. pneumophila in D. discoideum Ax3 but not in sey1 and of wild-type but not mutant bacteria lacking a homologue of the E. coli fatty acid transporter FadL. Finally, isotopologue profiling indicated that intracellular L. pneumophila metabolizes 13C-palmitate, and its catabolism was reduced in D. discoideum sey1 and L. pneumophila fadL. Taken together, our results reveal that Sey1 mediates LD- and FadL-dependent fatty acid metabolism of intracellular L. pneumophila

2023-06-07 | PXD038200 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data