Effects of CHCHD10 G58R and S59L mutations on global gene expression in the presence and absence of OMA1
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE189393 | GEO | 2022/06/30
REPOSITORIES: GEO
Similar Datasets
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
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 knocking down OMA1 by ASO in CHCHD10 G58R mouse model of mitochondrial myopathy/cardiomyopathy.
2024-07-13 | GSE271792 | GEO
Project description:Effects of acute OMA1 knockdown on global gene expression in CHCHD10 G58R mutants
| PRJNA782888 | ENA
Project description:Effects of CHCHD10 G58R and S59L mutations on global gene expression in the presence and absence of OMA1
| PRJNA782890 | ENA
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
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
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
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
Project description:Expression data from adult C10 G58R OMA1 KD mouse liver.
| PRJNA1133626 | ENA
Project description:The metabolic plasticity of mitochondria supports cell development and differentiation and ensures cell survival under stress. The peptidase OMA1 regulates mitochondrial morphology and stress signaling and orchestrates tumorigenesis and cell fate decisions in a cell and tissue-specific manner. Here, we have used unbiased systemic approaches to demonstrate that OMA1-dependent cell fate decisions are under metabolic control. A metabolism-focus CRISPR screen combined with an integrated analysis of human expression data unraveled a protective role of OMA1 against DNA damage. Nucleotide deficiencies induced by chemotherapeutic agents promote the selective, p53-dependent apoptosis of cells lacking OMA1. The protective effect of OMA1 does not depend on OMA1 activation nor on OMA1-mediated OPA1 and DELE1 processing. OMA1-deficient cells have reduced glycolytic capacity and accumulate OXPHOS proteins upon DNA damage. OXPHOS inhibition restores glycolysis and confers resistance against DNA damage. Thus, metabolic cues determine cell fate decisions by OMA1, which sheds new light on the role of OMA1 in cancerogenesis.
2023-04-04 | PXD036595 | Pride