Gene expression in a Drosophila model of mitochondrial disease.
<h4>Background</h4>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...
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oai:doaj.org-article:ffb2ebf584b74dfb90c7d31140c093222021-11-25T06:26:54ZGene expression in a Drosophila model of mitochondrial disease.1932-620310.1371/journal.pone.0008549https://doaj.org/article/ffb2ebf584b74dfb90c7d31140c093222010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20066047/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Daniel J M Fernández-AyalaShanjun ChenEsko KemppainenKevin M C O'DellHoward T JacobsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8549 (2010) |
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Medicine R Science Q Daniel J M Fernández-Ayala Shanjun Chen Esko Kemppainen Kevin M C O'Dell Howard T Jacobs Gene expression in a Drosophila model of mitochondrial disease. |
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<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
format |
article |
author |
Daniel J M Fernández-Ayala Shanjun Chen Esko Kemppainen Kevin M C O'Dell Howard T Jacobs |
author_facet |
Daniel J M Fernández-Ayala Shanjun Chen Esko Kemppainen Kevin M C O'Dell Howard T Jacobs |
author_sort |
Daniel J M Fernández-Ayala |
title |
Gene expression in a Drosophila model of mitochondrial disease. |
title_short |
Gene expression in a Drosophila model of mitochondrial disease. |
title_full |
Gene expression in a Drosophila model of mitochondrial disease. |
title_fullStr |
Gene expression in a Drosophila model of mitochondrial disease. |
title_full_unstemmed |
Gene expression in a Drosophila model of mitochondrial disease. |
title_sort |
gene expression in a drosophila model of mitochondrial disease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doaj.org/article/ffb2ebf584b74dfb90c7d31140c09322 |
work_keys_str_mv |
AT danieljmfernandezayala geneexpressioninadrosophilamodelofmitochondrialdisease AT shanjunchen geneexpressioninadrosophilamodelofmitochondrialdisease AT eskokemppainen geneexpressioninadrosophilamodelofmitochondrialdisease AT kevinmcodell geneexpressioninadrosophilamodelofmitochondrialdisease AT howardtjacobs geneexpressioninadrosophilamodelofmitochondrialdisease |
_version_ |
1718413720265162752 |