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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 31, 2024 |
| Title |
Expression data from P28 C10 G58R Dele1 mouse gastrocnemius muscles. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
16 total samples were analyzed (4 biological replicates of each of the 4 different genotypes). Genes with an FDR≤0.05 and a fold-change ≥2 were selected.
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| Web link |
https://doi.org/10.1038/s44318-024-00242-x
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| Contributor(s) |
Narendra D, Lin H |
| Citation(s) |
39379554 |
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| Submission date |
Jul 26, 2024 |
| Last update date |
Oct 30, 2024 |
| Contact name |
Narendra Derek |
| E-mail(s) |
derek.narendra@nih.gov
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| Phone |
301-594-4737
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| Organization name |
National Institutes of Health
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| Department |
National Institute of Neurological Disorders and Stroke
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| Lab |
Inherited Movement Disorders Unit, Neurogenetics Branch
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| Street address |
35 Convent Drive, Room 2A215
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20814 |
| Country |
USA |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (16)
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| GSM8423776 |
G58R Dele1 KO gastrocnemius at P28, biological rep1 |
| GSM8423777 |
G58R Dele1 + gastrocnemius at P28, biological rep1 |
| GSM8423778 |
C10WT Dele KO gastrocnemius at P28, biological rep1 |
| GSM8423779 |
C10WT Dele + gastrocnemius at P28, biological rep1 |
| GSM8423780 |
C10WT Dele KO gastrocnemius at P28, biological rep2 |
| GSM8423781 |
C10WT Dele KO gastrocnemius at P28, biological rep3 |
| GSM8423782 |
G58R Dele1 + gastrocnemius at P28, biological rep2 |
| GSM8423783 |
C10WT Dele + gastrocnemius at P28, biological rep2 |
| GSM8423784 |
G58R Dele1 KO gastrocnemius at P28, biological rep2 |
| GSM8423785 |
C10WT Dele + gastrocnemius at P28, biological rep3 |
| GSM8423786 |
G58R Dele1 + gastrocnemius at P28, biological rep3 |
| GSM8423787 |
G58R Dele1 KO gastrocnemius at P28, biological rep3 |
| GSM8423788 |
G58R Dele1 + gastrocnemius at P28, biological rep4 |
| GSM8423789 |
C10WT Dele KO gastrocnemius at P28, biological rep4 |
| GSM8423790 |
C10WT Dele + gastrocnemius at P28, biological rep4 |
| GSM8423791 |
G58R Dele1 KO gastrocnemius at P28, biological rep4 |
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| Relations |
| BioProject |
PRJNA1140581 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE273193_RAW.tar |
23.6 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
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