Study of the Role of Miro Mitochondrial Outer Membrane Protein in Drosophila Model of Alzheimers Disease

Abstract

Miro (mitochondrial Rho GTPases), a mitochondrial outer membrane protein, newlinefacilitates mitochondrial axonal transport along the microtubules to facilitate neuronal newlinefunction. It plays an important role in regulating mitochondrial dynamic (fusion and newlinefission) and cellular energy generation. Several studies have suggested that altered newlinemitochondrial function is one of the key pathologies associated with the onset of newlinevarious neurodegenerative diseases including Alzheimer s disease (AD). Being the sole mitochondrial membrane protein, Miro might play a crucial role in several newlineneurodegenerative diseases (NDs). Thus, in the present study, we have explored the newlinepossible genetic interaction between Miro and AD-related genes such as Tau, Aand#946;42 and Appl in Drosophila melanogaster. Our study has demonstrated that ectopic expression of Tau, Aand#946;42 and Appl induced AD-related pathologies such as rough eye phenotype, defect in phototaxis and climbing activity with a shortened lifespan in Drosophila. We observed these AD-related pathologies were decreased by overexpression of Miro in AD model flies genetic background. Overexpression of Miro decreased the rough eye phenotype, improved the behavioral activities (climbing and phototaxis) and increased the ATP level in AD model flies. Further, the improvement examined in AD-related phenotypes was correlated with decreased oxidative stress, reduced cell death and neurodegeneration in Miro overexpressing AD model flies. Thus, the newlineobtained results suggested that Miro genetically interacts with AD-related genes in Drosophila and has the potential to be used as a therapeutic target for the design of the therapeutic strategies for NDs. newline