Dmiro Interaction Screen

Abstract

Mitochondria and their role in ATP production are the backbone of energetic demands in living organisms. This demand is especially seen in neurons, brain cells with specialized processes like action potential propagation and neurotransmitter release. Neuronal high-energy demands make mitochondrial transport essential for neuronal function and survival. Although the importance of mitochondrial atypical Rho-like GTPase (Miro) for mitochondrial transport is known, many questions remain. The following genomic screen aimed to identify other proteins involved in the Miro pathway, testing for genetic interactions between heterozygous dmiro null mutations and heterozygous deficiencies (deletions) covering approximately 85% of the Drosophila genome. Using live time-lapse imaging of GFP-labeled mitochondria in motor axons of larval Drosophila nerves, mitochondrial flux, the number of mitochondria moving per minute, was examined for deficiencies either enhancing or suppressing the mitochondrial flux phenotype of heterozygous dmiro null mutations, suggesting interaction with the Miro signaling pathway. Significant differences from control were defined as "candidate deficiencies" and subjected to retests; these regions were narrowed down to "map" the modifier mutations to individual genes. A total of 38 deficiencies were identified to interact with Miro. Of these, 7 deficiencies were further mapped and 14 genes were identified as strong candidates for Mirointeracting genes.