A genetic deficiency screen in vivo reveals rescue mechanisms of mitochondrial dysfunction

The mitochondrial network forms a central hub in cellular metabolism, adapting to a vast array of environmental and cellular signals to maintain cellular homeostasis. Derangements to this network can lead to mitochondrial diseases but are also increasingly recognised to be a contributing factor in common disorders including heart failure, neurodegeneration, cancer, or the natural ageing process. Despite its central importance, little is known how the cell responds to a mitochondrial dysfunction, contributing to our lack of affective treatment strategies. Here we performed an unbiased genetic deficiency screen in the fruit fly to identify mechanisms that can rescue a lethal mitochondrial dysfunction. After screening ~40% of the fly genome, we identified 10 genes from four distinct cellular pathways that rescued the mitochondrial dysfunction upon heterozygous deletion, resulting in viable adult flies. The data presented here includes proteomic analysis of larvae of control, mutant, and rescued lines.