The AOX effect

You can see three tubes in the following video, each of which contains 10 flies – all alive. On the left (“controls”) , all flies comfortably climb upwards after being tapped down. These are unaffected flies. The ten flies in the middle (“COX def.”) , however, are too weak to climb, due to the lack a key protein in their nerve cells. The flies on the right (“COX def. + AOX”) also have the same deficiency, but they also have an additional protein called alternative oxidase (AOX) in the same cells, and now they can climb again (This experiment was previously published in the Scientific Reports journal).

Here is a quantification of the repeat experiment, also showing a dose-dependent effect. The y-axis, “Climbing index”, shows how well flies can climb. The controls can climb very comfortably, and AOX expression alone does not affect this. However flies with pan-neuronal cytochrome c oxidase (COX) deficiency are unable to climb without AOX. High levels of AOX expression in nerve cells dramatically rescues this phenotype. Lower levels of AOX in the same cells gives a milder (but statistically significant)  rescue. Finally, inactive AOX (inactived by mutations in its active center) does not help at all.

The effect of neuronal COX deficiency on locomotor abilities, and its rescue by AOX expression. Center lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles, data points are represented by dots. p<0.001, One-way ANOVA.

Using neuronal COX deficiency in Drosophila melanogaster as a disease model, I am studying how COX deficiency in neurons leads to locomotion problems. My focus is the type of neurons affected, and the pathological mechanisms by which they are affected. I also explore how AOX alleviates these phenotypes and processes.

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