Gene expression in a drosophila model of mitochondrial disease

Fernández-Ayala, D.J.M., Chen, S., Kemppainen, E., O'Dell, K.M.C. and Jacobs, H.T. (2010) Gene expression in a drosophila model of mitochondrial disease. PLoS ONE, 5(1), e8549. (doi: 10.1371/journal.pone.0008549)




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 tko25tmutant 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.

Item Type:Articles
Additional Information:This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glasgow Author(s) Enlighten ID:O'Dell, Professor Kevin
Authors: Fernández-Ayala, D.J.M., Chen, S., Kemppainen, E., O'Dell, K.M.C., and Jacobs, H.T.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Published Online:06 January 2010
Copyright Holders:© 2010 Fernandez-Ayala et al
First Published:First published in PLoS ONE 2010 5(1): e8549
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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