Expression data from P56 Ckmm-cre Tfam Dele1 mouse hearts
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1140582 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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
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:Expression data from P28 C10 G58R Dele1 mouse hearts
| PRJNA1140583 | ENA
Project description:Expression data from P140 C10 S59L Dele1 mouse hearts
| PRJNA1140577 | 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 transcription factor A (TFAM) was deleted in renal epithelial cells using the Six2-Cre transgene. To characterize gene expression in TFAM-deficient renal epithelial cells, renal cortices from mutant and Cre-negative control mice were compared.
2021-06-28 | GSE147189 | GEO
Project description:Osteoblasts require substantial amounts of energy to synthesize bone matrix and coordinate the mineralization of the skeleton. This study analyzed the effect of mitochondrial dysfunction on bone formation in mouse limbs. The limb mesenchyme-specific Tfam knockout (Tfamf/f;Prx1-Cre: Tfam-cKO) mice were analyzed morphologically, and histologically and gene expression in the limb bones were assessed by in situ hybridization, quantitative real-time PCR and RNA sequencing. Moreover, we analyzed mitochondrial function of osteoblasts in Tfam-cKO mice by mitochondrial membrane potential assay and transmission electron microscopic (TEM) observations. We investigated the pathogenesis of spontaneous bone fractures by immunohistochemical analysis, TEM observations and biomechanical examination. The forelimbs in Tfam-cKO mice were significantly shortened from birth and occurred spontaneous fractures within the first week after birth, resulting in severe limb deformities. Histologically, bone hypoplasia with decrease of matrix mineralization was apparent, and the expressions of type Ⅰ collagen and osteocalcin were decreased in the osteoblasts of Tfam-cKO mice although Runx2 expression was unchanged. Decreased type Ⅰ collagen deposition and mineralization in the matrix of the limb bones in Tfam-cKO mice was associated with marked mitochondrial dysfunction. Biomechanical analysis showed significantly lower Young’s modulus and hardness due to poor apatite orientation in the bone tissue of Tfam-cKO mice. The mice with limb mesenchyme-specific Tfam deletion exhibited spontaneous limb bone fractures, resulting in severe limb deformities. Their bone fragility was caused by poor apatite orientation due to impaired osteoblasts differentiation and maturation.
2023-03-24 | GSE196628 | GEO
Project description:The goal of this study was to compare the gene expression profiles of WT, Tfam+/-, Zbp1-/- and Tfam+/-Zbp1-/- MEFs.
2023-01-28 | GSE223553 | GEO