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| Status |
Public on Jan 12, 2010 |
| Title |
Gene expression in a Drosophila model of mitochondrial disease |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by array
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| Summary |
Background: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, provokes a phenotype of respiratory chain deficiency, developmental delay and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behaviour.
Results: Transcriptome-wide analysis of gene expression in tko25t mutant flies revealed systematic, compensatory changes in expression of genes connected with metabolism, including upregulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, the TCA cycle and anaplerotic pathways feeding into it. Gut-specific enzymes involved in the primary mobilization of dietary fat and protein, as well as a number of transport functions, were strongly upregulated, consistent with the idea that OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. Many stress-response genes were also induced. Other changes may reflect a signature of developmental delay. There was also down-regulation of genes connected with reproduction, including gametogenesis, especially in females, and courtship behaviour in males. This might represent a programmed response to a mitochondrially generated starvation signal. Although human sexual behaviour is not known to respond to mitochondrial dysfunction, the underlying signaling pathway, if conserved, could influence many physiological processes in response to nutritional stress. Transcriptomic analysis suggested the possible involvement of the Akt1/sgg signaling pathway(s).
Conclusions: The transformation of metabolism in response to mitochondrial dysfunction, including digestive and absorptive functions, gives important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.
Keywords: mutant analysis
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| Overall design |
Crosses and maintenance: Inbreeding under stressful conditions inevitably results in the selection of compensatory alleles of many genes. In order to avoid such issues, and thus determine the global effects on gene expression of the tko25t mutation in a truly unselected and 'wild-type' background, we outbred tko25t over more than 10 generations by back-crossing to each of two commonly used wild-type strains, Canton S and Oregon R. Subsequent to this backcrossing, tko25t was maintained in each background using a balancer chromosome. These stocks were then used to generate a tko25t mutant F1 generation, by crossing virgin Canton S tko25t homozygous mutant females with Oregon R tko25t males. For comparison, we generated otherwise isogenic wild-type F1 progeny by crossing virgin Canton S wild-type females with Oregon R wild-type males.
Samples: Both tko25t and wild-type Drosophila adult flies of both sexes were collected and aged to 1 day old prior to RNA extraction and hybridization on Affymetrix microarrays. We extracted RNA from 3 independent such crosses.
Comparative analysis: Data analysis for each gene in the array compared each tko25t mutant RNA isolate with each wild-type RNA isolate from flies of the given sex, generating 9 comparative measurements, over which the statistical analysis was performed.
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| Contributor(s) |
Fernández-Ayala DM, Chen S, Kemppainen E, O’Dell KM, Jacobs HT |
| Citation(s) |
20066047 |
| Submission date |
Jan 14, 2008 |
| Last update date |
Aug 28, 2018 |
| Contact name |
Daniel Jose Moreno Fernandez-Ayala |
| E-mail(s) |
dmorfer@upo.es
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| Organization name |
Universidad Pablo de Olavide
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| Lab |
CABD/CSIC-UPO
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| Street address |
Carretera de Utrera, Km. 1
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| City |
Sevilla |
| ZIP/Postal code |
41013 |
| Country |
Spain |
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| Platforms (1) |
| GPL1322 |
[Drosophila_2] Affymetrix Drosophila Genome 2.0 Array |
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| Samples (12)
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| GSM257061 |
male tko25t mutant, biological rep1 |
| GSM257062 |
male tko25t mutant, biological rep2 |
| GSM257063 |
male tko25t mutant, biological rep3 |
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| Relations |
| BioProject |
PRJNA108371 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10169_RAW.tar |
24.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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