Abstract | BACKGROUND: A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause 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 behavior. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a transcriptome-wide analysis of gene expression in tko(25t) mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stress-response genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified. CONCLUSIONS/SIGNIFICANCE: These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.
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Authors | Daniel J M Fernández-Ayala, Shanjun Chen, Esko Kemppainen, Kevin M C O'Dell, Howard T Jacobs |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 1
Pg. e8549
(Jan 06 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 20066047
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ribosomal Proteins
- ribosomal protein S12
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Topics |
- Animals
- Disease Models, Animal
- Drosophila
(genetics)
- Female
- Gene Expression
- Gene Expression Profiling
- Male
- Mitochondrial Diseases
(genetics)
- Oxidative Phosphorylation
- Point Mutation
- Ribosomal Proteins
(genetics)
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