Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from adult C10 G58R OMA1 KD mouse liver.

ABSTRACT: Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the Clariom_S_Mouse Microarray from Affymetrix/Applied Biosystems to analyze the effect of knocking down OMA1 by ASO in CHCHD10 G58R mouse model of mitochondrial myopathy/cardiomyopathy.

ORGANISM(S): Mus musculus

PROVIDER: GSE271792 | GEO | 2024/07/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from P28 C10 G58R Dele1 mouse gastrocnemius muscles.

Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the Clariom_S_Mouse Microarray from Affymetrix to analyze the effect of Dele1 KO in CHCHD10 G58R mouse model of mitochondrial myopathy/cardiomyopathy.

2024-07-31 | GSE273193 | GEO

Expression data from P28 C10 G58R Dele1 mouse hearts

Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the "Clariom S Assay, mouse" from Affymetrix/Applied Biosystems to analyze the effect of Dele1 KO in CHCHD10 G58R mouse model of mitochondrial myopathy/cardiomyopathy.

2024-07-31 | GSE273191 | GEO

Expression data from P140 C10 S59L Dele1 mouse hearts

Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the "Clariom S Assay, mouse" from Affymetrix/Applied Biosystems to analyze the effect of Dele1 KO in CHCHD10 S59L mouse model of mitochondrial myopathy/cardiomyopathy.

2024-07-31 | GSE273187 | GEO

Expression data from adult Dele1 and OMA1 mouse brown adipose tissues (BATs).

Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the Clariom_S_Mouse Microarray from Affymetrix/Applied Biosystems to analyze the effect of Dele1 KO and OMA1 KO under cold stress.

2024-07-31 | GSE273199 | GEO

Expression data from P56 Ckmm-cre Tfam Dele1 mouse hearts

Project description:Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1’s protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy. This experiment used the "Clariom S Assay, mouse" from Affymetrix/Applied Biosystems to analyze the effect of Dele1 KO in Ckmm-cre Tfam (Tfam mKO) mouse model of mitochondrial myopathy/cardiomyopathy.

2024-07-31 | GSE273192 | GEO

DELE1 mitochondrial integrated stress response to CHCHD10 G58R protein misfolding in striated muscle [RNA-seq]

Project description:Transcriptional mitochondrial stress response to CHCHD10 G58R protein misfolding in mouse heart, gastrocnemius, and tibalis anterior muscle the presence and absence of the DELE1 mitochondrial integrated stress responses

2024-07-31 | GSE273310 | GEO

Effects of acute OMA1 knockdown on global gene expression in CHCHD10 G58R mutants

Project description:Differential gene expression in CHCHD10 G58R mouse hearts treated with nontargeting or OMA1-targeting antisense oligomers (ASOs) provided by Ionis Pharmaceuticals (Carlsbad, CA) This experiment used the Clariom_S_Mouse Microarray from Affymetrix to analyze the effect of acute OMA1 KD on gene expression in CHCHD10 G58R mouse hearts.

2022-06-30 | GSE189396 | GEO

Mouse heart proteomics in Oma1 and Cox10 deficient mice

Project description:Cardiomyopathy and heart failure are common manifestations in mitochondrial disease caused by deficiencies in the oxidative phosphorylation system of mitochondria (OXPHOS). Here, we demonstrate that the cardiac-specific loss of the assembly factor Cox10 of the cytochrome c oxidase causes mitochondrial cardiomyopathy in mice, which is associated with OXPHOS deficiency, lysosomal defects and an aberrant mitochondrial morphology and ultrastructure. We demonstrate activation of the mitochondrial peptidase Oma1 in Cox10-/- mice, which results in mitochondrial fragmentation and induction of the integrated stress response (ISR) along the Oma1-Dele1-Atf4 signalling axis. Ablation of Oma1 or Dele1 in Cox10-/- mice aggravates cardiomyopathy. ISR inhibition impairs the cardiac glutathione metabolism, decreases the levels of the glutathione peroxidase Gpx4 and increases lipid peroxidation in the heart, ultimately culminating in ferroptosis. Our results demonstrate a protective role of the Oma1-mediated ISR in mitochondrial cardiomyopathy and link ferroptosis to OXPHOS deficiency and mitochondrial disease.

2022-07-27 | PXD031641 | Pride

DELE1 mitochondrial integrated stress response to CHCHD10 G58R protein misfolding in striated muscle [RNA-seq]

Project description:DELE1 mitochondrial integrated stress response to CHCHD10 G58R protein misfolding in striated muscle [RNA-seq]

| PRJNA1141402 | 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

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