Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [ATAC-seq]

ABSTRACT: In this study, we show that within minutes of exposure to differentiation cues and activation of the electron transport chain, the mitochondrial outer membrane transiently fuses with the nuclear membrane of neural progenitors, leading to efflux of the nuclear-encoded RNAs (neRNA) into the positively charged mitochondrial intermembrane space. Subsequent degradation of mitochondrial neRNAs by Polynucleotide phosphorylase 1 (Pnpt1) residing in the intermembrane space curbs the transcriptomic memory of progenitor cells. Further, phosphorolysis by Pnpt1 indirectly suppresses ATP production by depriving ATP synthase of inorganic phosphate, resulting in delayed recovery of the attenuated transcriptomic memory. Collectively, these events force the progenitor cells towards a “tipping point” characterised by emergence of a competing neuronal differentiation program.

ORGANISM(S): Mus musculus

PROVIDER: GSE229489 | GEO | 2024/11/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE229489_TSS-ATACseq.csv.gz	Csv

Items per page:

1 - 2 of 2

Similar Datasets

Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [RNA-seq]

Project description:In this study, we show that within minutes of exposure to differentiation cues and activation of the electron transport chain, the mitochondrial outer membrane transiently fuses with the nuclear membrane of neural progenitors, leading to efflux of the nuclear-encoded RNAs (neRNA) into the positively charged mitochondrial intermembrane space. Subsequent degradation of mitochondrial neRNAs by Polynucleotide phosphorylase 1 (Pnpt1) residing in the intermembrane space curbs the transcriptomic memory of progenitor cells. Further, phosphorolysis by Pnpt1 indirectly suppresses ATP production by depriving ATP synthase of inorganic phosphate, resulting in delayed recovery of the attenuated transcriptomic memory. Collectively, these events force the progenitor cells towards a “tipping point” characterised by emergence of a competing neuronal differentiation program.

2024-11-14 | GSE229490 | GEO

Drosophila CNS mitochondrial DNA dysfunction microarray

Project description:Mitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. ATP synthase is Complex V of the mitochondrial respiratory chain. It is driven by a proton gradient between the intermembrane space and the mitochondrial matrix and generates the majority of cellular ATP. The knockdown of coupling factor 6 (Cf6), one of the components of the proton channel F0, causes dysfunction in the complex, leading to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level.

2013-12-20 | GSE53509 | GEO

CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex

Project description:CLPB is a mitochondrial intermembrane space AAA+ domain–containing disaggregase. CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia; however, the molecular mechanism underscoring disease and the contribution of CLPB substrates to disease pathology remains unknown. Interactions between CLPB and mitochondrial quality control (QC) factors, including PARL and OPA1, have been reported, hinting at dysregulation of organelle QC in disease. Utilizing proteomic and biochemical approaches, we define a stress-specific aggregation phenotype in a CLPB-null environment and define the CLPB substrate profile. We show an interplay between intermembrane space proteins including CLPB, HAX1, HTRA2, and the inner membrane quality control proteins (STOML2, PARL, YME1L1; SPY complex), with CLPB deficiency impeding SPY complex function by virtue of protein aggregation in the intermembrane space. We conclude that there is an interdependency of mitochondrial QC components at the intermembrane space/inner membrane interface, and perturbations to this network may underscore CLPB disease pathology.

2024-01-18 | PXD042313 | Pride

Disrupting mitochondrial copper distribution inhibits leukemic stem cell self-renewal

Project description:Leukemic stem cells (LSC) rely on oxidative metabolism and are differentially sensitive to targeting mitochondrial pathways, which spares normal hematopoietic cells. A subset of mitochondrial proteins are folded in the intermembrane space via the mitochondrial intermembrane assembly (MIA) pathway. We found increased mRNA expression of MIA pathway substrates in acute myeloid leukemia (AML) stem cells. Therefore, we evaluated the effects of inhibiting this pathway in AML. Genetic and chemical inhibition of ALR reduces AML growth and viability, disrupts LSC self-renewal and induces their differentiation. ALR inhibition preferentially decreases its substrate COX17, a mitochondrial copper chaperone and knockdown of COX17 phenocopies ALR loss. Inhibiting ALR and COX17 increases mitochondrial copper levels which in turn inhibit S-Adenosylhomocysteine Hydrolase (SAHH) and lower levels of S-adenosylmethionine (SAM), DNA methylation, and chromatin accessibility to lower LSC viability. These results provide insight into mechanisms through which mitochondrial copper controls epigenetic status and viability of LSCs.

2020-04-14 | GSE146252 | GEO

Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space

Project description:Mitochondria are complex organelles with different compartments, each harboring their own protein quality control factors. While the chaperones of the mitochondrial matrix have been well characterized, it is poorly understood which chaperones protect the mitochondrial intermembrane space. We show that cytosolic small heat shock proteins are imported under basal conditions into the mitochondrial intermembrane space, where they operate as molecular chaperones. To identify chaperone substrates with MS/MS, we used a molecular trap variant of HSPB1/Hsp27 (S135F mutant). Through affinity-enrichment co-immunoprecipitation we identified significantly enriched substrates versus GFP-negative control.

2022-12-12 | PXD038275 | Pride

Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenioptors

Project description:Recent studies have linked bioenergetic regulation to cellular differentiation. However, the contribution of metabolic communication among subcellular components to the fate of progenitor cells remains unclear. Adenylate kinase 2 (AK2) is an adenylate phosphotransferase localized in the mitochondrial intermembrane space. Although AK2 mutations in human can cause a severe combined immunodeficiency with neutropenia, named reticular dysgenesis (RD), underlying mechanisms have not yet been elucidated. To address these questions, we established induced pluripotent stem cells (iPSCs) from two RD patients. Metabolic flux analysis revealed that AK2 mediates the distribution of glycolytic metabolites into the tricarbon acid cycle in mitochondria. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. Intriguingly, RD-iPSC-derived hematopoietic progenitors exhibited an immature mitochondrial morphology, discordant ATP distribution among the mitochondria and nucleus, and alteration of global transcriptional profiles. These results highlight the importance of stage-specific intracellular energy communication for controlling the fate of multipotential progenitors.

2018-09-03 | GSE76761 | GEO

OXPHOS deficiency activates global adaptation pathways to maintain mitochondrial membrane potential

Project description:Reduction of mitochondrial membrane potential is a hallmark of mitochondrial dysfunction. It activates adaptive responses in organisms from yeast to human to rewire metabolism, remove depolarized mitochondria, and degrade unimported precursor proteins. It remains unclear how cells maintain mitochondrial membrane potential, which is critical for maintaining iron-sulfur cluster (ISC) synthesis, an indispensable function of mitochondria. Here we show that yeast oxidative phosphorylation mutants deficient in complex III, IV, V, and mtDNA respectively, have graded reduction of mitochondrial membrane potential and proliferation rates. Extensive omics analyses of these mutants show that accompanying mitochondrial membrane potential reduction, these mutants progressively activate adaptive responses, including transcriptional downregulation of ATP synthase inhibitor Inh1 and OXPHOS subunits, Puf3-mediated upregulation of import receptor Mia40 and global mitochondrial biogenesis, Snf1/AMPK-mediated upregulation of glycolysis and repression of ribosome biogenesis, and transcriptional upregulation of cytoplasmic chaperones. These adaptations disinhibit mitochondrial ATP hydrolysis, remodel mitochondrial proteome, and optimize ATP supply to mitochondria to convergently maintain mitochondrial membrane potential, ISC biosynthesis, and cell proliferation.

2020-11-27 | GSE162197 | GEO

Microarray of heterozygous deletion mutants of yeast ARH1, ATM1, YFH1, and HO (control) genes

Project description:We investigated the transcriptional response of yeast to the loss of a single copy of ARH1; an oxidoreductase of the mitochondrial inner membrane, which is among the few mitochondrial proteins that is essential for viability in yeast, ATM1; the mitochondrial inner membrane ATP-binding cassette (ABC) transporter, and of YFH1; the mitochondrial matrix iron chaperone, which oxidizes and stores iron, and interacts with Isu1p to promote Fe-S cluster assembly.

2019-08-13 | E-MTAB-7648 | biostudies-arrayexpress

Mitochondrial dsRNA triggers antiviral signalling in humans

Project description:Mitochondria are descendants of endosymbiotic bacteria and retain essential prokaryotic features such as a compact circular genome. Consequently, in mammals, mitochondrial DNA is subjected to bidirectional transcription that generates overlapping transcripts capable of forming long double-stranded RNA structures. However, to our knowledge, mitochondrial double-stranded RNA has not been previously characterized in vivo. Here, we describe the presence of a highly unstable native mitochondrial double-stranded RNA species at single cell level and identify keyroles for the degradosome components, mitochondrial dsRNA helicase SUV3 and polynucleotide phosphorylase PNPase in restricting the levels of mitochondrial double-stranded RNA. Loss of either enzyme results in massive accumulation of mitochondrial double-stranded RNA that escapes into the cytoplasm in a PNPase-dependent manner. This process engages an MDA5-driven antiviral signalling pathway that triggers a type I interferon response. Consistent with these data, patients carrying hypomorphic mutations in the gene PNPT1, which encodes PNPase, display mitochondrial double-stranded RNA accumulation coupled with upregulation of interferon-stimulated genes and other markers of immune activation. The localization of PNPase to the mitochondrial inter-membrane space and matrix suggests that it has a dual role in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This in turn prevents the activation of potent innate immune defence mechanisms evolved to protect vertebrates against microbial and viral attack.

2018-05-03 | GSE94957 | GEO

Mapping the protein interactome of mitochondrial intermembrane space proteases identifies a novel function for HTRA2

Project description:Data contains LC-MS data of proximity-based biotin labeling assay (BioID) to generate the protein interaction network of mitochondrial intermembrane space proteases fused with BirAFlag (C-terminal tag) and expressed in T-REx HEK293 cells.

2018-11-14 | MSV000083140 | MassIVE

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