Gene Expression in a Drosophila Model of Mitochondrial Disease

• DOI: 10.1371/journal.pone.0008549
• Publication Date: 2010-01-05T21:23:13Z
• Authors: Daniel J. M. Fern...; Shanjun Chen; Esko Kemppainen; Kevin M. C. O'Dell; Howard T. Jacobs
• Keywords: Male; Ribosomal Proteins; 0301 basic medicine; 570; Mitochondrial Diseases; Science; Gene Expression Profiling; Q; R; Gene Expression; Oxidative Phosphorylation; Disease Models, Animal; 03 medical and health sciences; Lääketieteen bioteknologia - Medical biotechnology; Medicine; Animals; Point Mutation; Drosophila; Female; Research Article

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 those presented many human mitochondrial disorders, as well defective courtship behavior.Here, we describe transcriptome-wide analysis expression tko(25t) mutant flies that revealed systematic compensatory changes genes connected with metabolism, including up-regulation lactate dehydrogenase involved catabolism fats proteins, various anaplerotic pathways. Gut-specific enzymes primary mobilization dietary number transport functions, were also strongly up-regulated, consistent idea oxidative phosphorylation OXPHOS dysfunction is perceived physiologically starvation for particular biomolecules. In addition, stress-response induced. Other may reflect signature notably down-regulation reproduction, gametogenesis, behavior males; logically this represents programmed response mitochondrially generated signal. The underlying signalling pathway, if conserved, could influence physiological processes nutritional stress, although any such pathway remains unidentified.These studies indicate general organ-specific metabolism transformed dysfunction, digestive absorptive give important clues how novel therapeutic strategies disorders might be developed.