Gene Expression in a Drosophila Model of Mitochondrial Disease


Näytä suppeat kuvailutiedot Fernandez-Ayala, Daniel JM - Chen, Shanjun - Kemppainen, Esko - O'Dell, Kevin MC - Jacobs, Howard T - 2012-06-17T20:14:31Z 2012-06-12 02:45:04 - 2012-06-17T20:14:31Z 2010 -
dc.identifier.issn 1932-6203 -
dc.description Public Library of Science -
dc.description.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 tko25t 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. -
dc.language.iso en -
dc.title Gene Expression in a Drosophila Model of Mitochondrial Disease -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-689 -
dc.identifier.doi 10.1371/journal.pone.0008549 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Lääketieteen bioteknologia | en=Medical biotechnology| -
dc.journal.title PLoS ONE -
dc.journal.volume 5 -
dc.journal.number 1 -
dc.journal.volumepagerange 1-17 -
dc.oldstats 61 -

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