Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A cooperative organelle biogenesis program in mammalian cells

ABSTRACT: The compartmentalisation of distinct organelles within eukaryotic cells is essential for their diverse functions, however, how their structures and functions depend on each other has not been systematically explored. We combined a fluorescent reporter of mitochondrial stress with genome-wide CRISPR knockout screening and identified networks of genes involved in the biogenesis and metabolism of diverse organelles. Targeted organelle gene knockouts identified that defects in peroxisomes, Golgi, and ER cause mitochondrial fragmentation and dysfunction. Correlative light and electron microscopy analysed using artificial intelligence-directed voxel extraction revealed in unprecedented detail how impaired mitochondrial interactions with diverse organelles caused cell-wide defects in their morphology and biogenesis. Multi-omics analyses identified a unified proteome stress response and global shifts in lipid and glycoprotein homeostasis that are elicited when organelle biogenesis is compromised. Our comprehensive resource has defined metabolic and morphological interactions between organelles that can be mined to understand how changes in organelle components drive diverse cellular pathologies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201573 | GEO | 2023/10/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A cooperative organelle biogenesis program in mammalian cells

Project description:The compartmentalisation of distinct organelles within eukaryotic cells is essential for their diverse functions, however, how their structures and functions depend on each other has not been systematically explored. We combined a fluorescent reporter of mitochondrial stress with genome-wide CRISPR knockout screening and identified networks of genes involved in the biogenesis and metabolism of diverse organelles. Targeted organelle gene knockouts identified that defects in peroxisomes, Golgi, and ER cause mitochondrial fragmentation and dysfunction. Correlative light and electron microscopy analysed using artificial intelligence-directed voxel extraction revealed in unprecedented detail how impaired mitochondrial interactions with diverse organelles caused cell-wide defects in their morphology and biogenesis. Multi-omics analyses identified a unified proteome stress response and global shifts in lipid and glycoprotein homeostasis that are elicited when organelle biogenesis is compromised. Our comprehensive resource has defined metabolic and morphological interactions between organelles that can be mined to understand how changes in organelle components drive diverse cellular pathologies.

2023-10-04 | PXD033871 | Pride

Peroxisome function relies on organelle-associated mRNA translation

Project description:Crucial metabolic functions of peroxisomes rely on a variety of peroxisomal membrane proteins (PMPs). While mRNA transcripts of PMPs were shown to be colocalized with peroxisomes, the process by which PMPs efficiently couple translation with targeting to the peroxisomal membrane remained elusive. Here, we combine quantitative electron microscopy with proximity-specific ribosome profiling and reveal that translation of specific PMPs occurs on the surface of peroxisomes in the yeast Saccharomyces cerevisiae. This places peroxisomes alongside chloroplasts, mitochondria, and the endoplasmic reticulum as organelles that use localized translation for ensuring correct insertion of hydrophobic proteins into their membranes. Moreover, the correct targeting of these transcripts to peroxisomes is crucial for peroxisomal and cellular function, emphasizing the importance of localized translation for cellular physiology.

2022-01-12 | GSE113567 | GEO

Mitochondrial-nuclear DNA interactions contribute to the regulation of nuclear transcript levels as part of the inter-organelle communication system

Project description:Nuclear and mitochondrial organelles must maintain a communication system. Loci on the mitochondrial genome were recently reported to interact with nuclear loci. To determine whether this is part of a DNA based communication system we used genome conformation capture to map the global network of DNA-DNA interactions between the mitochondrial and nuclear genomes (Mito-nDNA) in Saccharomyces cerevisiae cells grown under three different metabolic conditions. The interactions that form between mitochondrial and nuclear loci are dependent on the metabolic state of the yeast. Moreover, the frequency of specific mitochondrial - nuclear interactions (i.e. COX1-MSY1 and Q0182-RSM7) showed significant reductions in the absence of mitochondrial encoded reverse transcriptase machinery. Furthermore, these reductions correlated with increases in the transcript levels of the nuclear loci (MSY1 and RSM7). We propose that these interactions represent an inter-organelle DNA mediated communication system and that reverse transcription of mitochondrial RNA plays a role in this process. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.

2013-01-17 | E-GEOD-34132 | biostudies-arrayexpress

Mitochondrial-nuclear DNA interactions contribute to the regulation of nuclear transcript levels as part of the inter-organelle communication system

2013-01-17 | GSE34132 | GEO

Sequential lipidomic, metabolomic, and proteomic analyses of serum, liver, and heart tissue specimens from peroxisomal biogenesis factor 11α knockout mice

Project description:Peroxisomes are versatile single membrane-enclosed cytoplasmic organelles, involved in reactive oxygen species (ROS) and lipid metabolism and diverse other metabolic processes. Peroxisomal disorders result from mutations in Pex genes-encoded proteins named peroxins (PEX proteins) and single peroxisomal enzyme deficiencies. The PEX11 protein family (α, β, and γ isoforms) plays an important role in peroxisomal proliferation and fission. However, their specific functions and the metabolic impact caused by their deficiencies have not been precisely characterized. To understand the systemic molecular alterations caused by peroxisomal defects, here we utilized untreated peroxisomal biogenesis factor 11α knockout (Pex11α KO) mouse model and performed serial relative-quantitative lipidomic, metabolomic, and proteomic analyses of serum, liver, and heart tissue homogenates. We demonstrated significant specific changes in the abundances of multiple lipid species, polar metabolites, and proteins and dysregulated metabolic pathways in distinct biological specimens of the Pex11α KO adult mice in comparison to the wild type (WT) controls. Overall, the present study reports comprehensive semi-quantitative molecular omics information of the Pex11α KO mice, which might serve in the future as a reference for a better understanding of the roles of Pex11α and underlying pathophysiological mechanisms of peroxisomal biogenesis disorders.

2022-02-02 | MTBLS1887 | MetaboLights

A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders

Project description:Human peroxisome biogenesis disorders are lethal genetic disease in which abnormal peroxisome assembly compromises overall peroxisome and cellular function. Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes, notably lipid metabolism and the use of reactive oxygen species for detoxification. Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly. We also demonstrate the relevance of Drosophila as a genetic model for the early developmental defects associated with the human peroxisome biogenesis disorders. Mutation of the PEX1 gene is the most common cause of peroxisome biogenesis disorders and is one of the causes of the most severe form of the disease, Zellweger syndrome. Inherited mutations in Drosophila Pex1 correlate with reproducible defects during early development. Notably, Pex1 mutant larvae exhibit abnormalities that are analogous to those exhibited by Zellweger syndrome patients, including developmental delay, poor feeding, severe structural abnormalities in the peripheral and central nervous systems, and early death. Finally, microarray analysis defined clusters of genes whose expression varied significantly between wild-type and mutant larvae, implicating peroxisomal function in neuronal development, innate immunity, lipid and protein metabolism, gamete formation, and meiosis. Expression profiles were analyzed in triplicate from whole larvae of wild-type and pex1 homozygous mutant Drosophila.

2011-07-02 | E-GEOD-30362 | biostudies-arrayexpress

Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse Model of Metabolic Syndrome.

Project description:Purpose: MetS consist of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e. mitochondria and peroxisomes. Experimental design: The New Zealand Obese (NZO) mouse model exhibits a polygenic syndrome of obesity, insulin resistance, triglyceridemia and hypercholesterolemia that resembles human metabolic syndrome. We applied a combinatorial approach of lipidomics with liver transcriptomics, 2D-DIGETM and mass spectroscopy based organelle proteomics of highly purified mitochondria and peroxisomes in male mice, to investigate molecular mechanisms related to the impact of lipid metabolism in the pathophysiology of the metabolic syndrome. Conclusions and clinical relevance: Proteome analyses of liver organelles indicated differences in fatty acid metabolism, oxidative stress and response, mainly influenced by PG-C1α/PPARα mediated pathways. These results were in accordance with serum lipid profiles and elevated organelle functionality. These data emphasize that metabolic syndrome is accompanied with increased mitochondria and peroxisomal activity controlling directly cellular energy homeostasis to cope with dyslipidemia and hypercholesterinemia driven hepatic lipid overflow in developing a fatty liver.

2017-11-01 | GSE95489 | GEO

Charting Organellar Importomes by Quantitative Mass Spectrometry - ERV1 organelle-enriched fractions

Project description:Protein import into organelles is essential for all eukaryotes and facilitated by multi-protein translocation machineries. Analyzing whether a protein is transported into an organelle is largely restricted to single constituents. This renders knowledge about imported proteins incomplete, limiting our understanding of organellar biogenesis and function. Here, we introduce a method that enables to chart an organelle’s importome. Our method relies on inducible RNAi-mediated knockdown of an essential subunit of a translocase to impair import, metabolic labeling and quantitative mass spectrometry. To highlight its potential, we established the mitochondrial importome of Trypanosoma brucei, comprising 1,120 proteins including 331 new candidates. An exciting feature of this method is that it overcomes limitations in identifying proteins with dual or multiple locations. We demonstrate the specificity and versatility of this novel ImportOmics method by targeting import machineries in mitochondria and glycosomes demonstrating its high potential for globally studying protein import and inventories of organelles.

2017-06-14 | PXD005730 | Pride

ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells

Project description:Loss of organelle homeostasis is a hallmark of aging. However, it remains elusive how this occurs at transcriptional levels. Here, we report that human mesenchymal stem cell (hMSC) aging is associated with dysfunction of double-membrane organelles and downregulation of transcription factor ATF6. CRISPR/Cas9-mediated inactivation of ATF6 in hMSCs, not in human embryonic stem cells (hESCs), resulted in premature cellular aging, characteristic of loss of endomembrane homeostasis. Comparative transcriptomic analyses in hMSCs identify 145 constitutive and 112 tunicamycin-induced ATF6-regulated genes implicated in different layers of cellular homeostasis regulation. Notably, FOS was identified as one of the constitutive ATF6 responsive genes, downregulation of which contributes to accelerated hMSC senescence. Our study identifies a novel transcriptional program related to homeostatic regulation of membrane organelles, and provides mechanistic insights into aging-associated attrition of human stem cells.

2018-01-11 | GSE102004 | GEO

Peroxisomal retrograde signaling in C. elegans

Project description:Distinct retrograde signaling pathways have been identified for several cellular organelles. These pathways are important to maintain the function of these organelles in response to organelle-specific stress. Using Caenorhabditis elegans, we show for the first time that such a retrograde signaling also exists for peroxisomes. Analysis of the C. elegans transcriptome revealed that peroxisomal import stress caused by the knock-down of the peroxisomal matrix protein import receptor prx-5/PEX5 induces the compensatory up-regulation of genes involved in defense response and lipid metabolic processes, especially peroxisomal beta oxidation. We, therefore, propose that the peroxisomal retrograde signaling participates in the maintenance of peroxisomal function in response to peroxisomal import stress.

2020-12-19 | GSE156318 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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