Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell

ABSTRACT: Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell

PROVIDER: PRJNA546570 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR9204000_1.fastq.gz	Fastqsanger.gz
	SRR9204000_2.fastq.gz	Fastqsanger.gz
	SRR9204010_1.fastq.gz	Fastqsanger.gz
	SRR9204010_2.fastq.gz	Fastqsanger.gz
	SRR9204020_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 384

Similar Datasets

Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell

Project description:Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH oxidation to trace mechanisms linking different forms of mitochondrial dysfunction to the ISR in proliferating mouse myoblasts and in differentiated myotubes. In myoblasts, we find that impaired NADH oxidation upon electron transport chain (ETC) inhibition depletes asparagine, activating the ISR via the eIF2α kinase GCN2. In myotubes, however, impaired NADH oxidation following ETC inhibition neither depletes asparagine nor activates the ISR, reflecting an altered metabolic state. ATP synthase inhibition in myotubes triggers the ISR via a distinct mechanism related to mitochondrial inner-membrane hyperpolarization. Our work dispels the notion of a universal path linking mitochondrial dysfunction to the ISR, instead revealing multiple paths that depend both on the nature of the mitochondrial defect and on the metabolic state of the cell.

2020-05-27 | GSE132234 | GEO

Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell.

| S-EPMC7255802 | biostudies-literature

mtDNA breaks compromise mitochondrial membrane ultrastructure and trigger an integrated stress response

Project description:mtDNA breaks compromise mitochondrial membrane ultrastructure and trigger an integrated stress response

| PRJNA885786 | ENA

mtDNA breaks compromise mitochondrial membrane ultrastructure and trigger an integrated stress response

Project description:Mitochondrial DNA (mtDNA) breaks are deleterious lesions that lead to degradation of mitochondrial genomes and subsequent reduction in mtDNA copy number. The signaling pathways activated in response to mtDNA damage remain ill-defined. Using mitochondrial targeted restriction enzymes, we show that cells with mtDNA breaks exhibit reduced respiratory complexes, loss of membrane potential, and mitochondrial protein import defect. Furthermore, mtDNA damage activates the integrated stress response (ISR) through phosphorylation of eIF2α by the OMA1-DELE1-HRI pathway. Electron microscopy reveals concomitant defects in mitochondrial membranes and cristae ultrastructure. Notably, inhibition of the ISR exacerbates mitochondrial defects and delays the recovery of mtDNA copy number, thereby implicating this stress response in mitigating mitochondrial dysfunction following mtDNA damage. Last, we provide evidence suggesting that ATAD3A, a membrane-anchored protein that interacts with nucleoids, relays the signal from mtDNA breaks to the inner mitochondrial membrane. Altogether, our study fully delineates the sequence of events linking damaged mitochondrial genomes with the cytoplasm and uncovers an unanticipated role for the ISR in response to mitochondrial genome instability.

2022-10-04 | GSE214512 | GEO

Integrated analysis of transcriptional and metabolic responses to mitochondrial stress

Project description:Mitochondrial stress arises from a variety of sources, including accumulation of mutations in mitochondrial DNA, generation of reactive oxygen species, and insufficient supplies of oxygen or fuel. Cells utilize multiple pathways to respond to mitochondrial injury, including mitophagy, mitochondrial fusion, and the integrated stress response / mitochondrial unfolded protein response. However, the integration of transcriptional and metabolic signatures of distinct types of mitochondrial stress are still not well defined. We defined how primary human fibroblasts respond to a panel of well-characterized inhibitors that target key pathways in the mitochondria, using sub-lethal doses to trigger adaptive stress responses. By combining metabolomic and transcriptomic analyses, we established integrated signatures of mitochondrial stress. We developed a tool, SQUID, to infer molecular triggers of mitochondrial dysfunction in other datasets. Using SQUID, we globally investigated mitochondrial stress in the TCGA PanCancer Atlas and identified defects in pyruvate import in IDH1 mutant glioma. Altogether, these studies provide a comprehensive resource detailing cellular stress responses that safeguard mitochondrial health.

2025-04-14 | GSE241261 | GEO

A MITOCHONDRIAL STRESS RESPONSE TRIGGERED BY DEFECTS IN PROTEIN SYNTHESIS QUALITY CONTROL

Project description:Quality control defects of mitochondrial nascent chain synthesis trigger a sequential stress response characterised by OMA1 activation and ribosome decay, determining mitochondrial form and function.

2019-01-23 | PXD012416 | Pride

mtDNA breaks compromise mitochondrial membrane ultrastructure and trigger an integrated stress response

Project description:Mitochondrial DNA (mtDNA) breaks are toxic lesions that lead to degradation of mitochondrial genomes and subsequent reduction in mtDNA copy number. The signaling pathways activated in response to mtDNA damage remain poorly understood. We reasoned that factors that sense mtDNA damage are likely to be recruited to nucleoids shortly after break formation, prompting us to develop a proteomic-based approach to survey the interactome of mitochondrial nucleoids. Specifically, we combined proximity-dependent biotin labeling with Stable Isotope Labeling by Amino acids in Cell culture (SILAC) and tandem mass spectrometry. We used mitochondrial targeted restriction enzymes for the proximity probe and show that cells with mtDNA breaks exhibit reduced respiratory complexes, loss of membrane potential, and mitochondrial protein import defect. Notably, mtDNA breaks activate the integrated stress response (ISR) through phosphorylation of eIF2a by the OMA1-DELE1-HRI pathway. Inhibition of the ISR exacerbates mitochondrial defects and delays the recovery of mtDNA copy number, hinting at a role for the ISR in mitigating mitochondrial dysfunction following mtDNA damage. Electron microscopy reveals defective mitochondrial membranes and cristae ultrastructure. Last, we highlight a potential role for ATAD3A - a protein that is anchored to the inner mitochondrial membrane while interacting with nucleoids - in relaying the signal from damaged mtDNA to the mitochondrial inner membrane. Altogether, our study delineates the sequence of events linking damaged mitochondrial genomes to the cytoplasmic stress response. The mass spectrometry raw files for the combined SILAC and proximity-dependent biotin labeling experiment are deposited here.

2022-10-05 | MSV000090459 | MassIVE

Dm Trigger Hair

Project description:RNAseq analysis of the Dionaea muscipula trigger hair

| PRJEB38423 | ENA

Kids First: Congenital Heart Defects and Laterality Birth Defects

Project description:Kids First: Congenital Heart Defects and Laterality Birth Defects

| PRJNA760554 | ENA

Kids First: Congenital Heart Defects and Laterality Birth Defects

Project description:Kids First: Congenital Heart Defects and Laterality Birth Defects

| PRJNA760555 | ENA