Effects of acute OMA1 knockdown on global gene expression in CHCHD10 G58R mutants
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ABSTRACT:
PROVIDER: PRJNA782888 | ENA |
REPOSITORIES: ENA
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:Differential gene expression in CHCHD10 mutants with OMA1 present or knocked out This experiment used the Clariom_S_Mouse Microarray from Affymetrix to analyze the effect of CHCHD10 mutations on gene expression, and the effect of congenital OMA1 KO on gene expression in these CHCHD10 mutants.
2022-06-30 | GSE189393 | 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:Mutations in CHCHD10, a mitochondrial protein implicated in proteostasis and cristae maintenance, cause autosomal dominant mitochondrial diseases characterized by cardiomyopathy and neurodegeneration. Heterozygous Chchd10 S55L knock-in mice (modeling the human S59L variant) develop progressive mitochondrial cardiomyopathy driven by CHCHD10 aggregation, which is associated with chronic activation of the mitochondrial integrated stress response (mtISR). Here, we demonstrate that cardiac dysfunction is affected by biological sex and is associated with dual defects originating at the onset of disease: (1) early respiratory chain failure linked to cytochrome c depletion and impaired copper homeostasis and (2) maladaptive mtISR signaling via the OMA1-DELE1-HRI axis. Genetic inactivation of OMA1 delays cardiomyopathy without rescuing CHCHD10 insolubility, proteomic remodeling, cristae defects or OXPHOS impairment, demonstrating that mtISR can be uncoupled from the bioenergetic collapse triggered by CHCHD10 protein aggregation. Proteomic profiling of soluble and insoluble mitochondrial proteins reveals wide-spread disruptions of mitochondrial proteostasis, including IMS proteins involved in cytochrome c biogenesis. Defective respiration in mutant mitochondria could be rescued by the exogenous addition of cytochrome c, pinpointing IMS proteostasis disruption as a key pathogenic mechanism. Our work reveals that CHCHD10 insolubility and aggregation compromises metabolic resilience by impairing both electron transport and stress adaptation within the IMS, offering new perspectives for the development of therapeutic targets. This repository contains the heart whole proteome of the four different genotypes. a) whole proteome dataset is indicated by the identifier: KmUUbGabck
2025-11-07 | PXD064045 | Pride
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: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 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: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:Expression data from adult C10 G58R OMA1 KD mouse liver.
| PRJNA1133626 | 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/Applied Biosystems to analyze the effect of Dele1 KO and OMA1 KO under cold stress.
2024-07-31 | GSE273199 | GEO