Effects on Dopaminergic Neurons Are Secondary in COX-Deficient Locomotor Dysfunction in Drosophila
Cagri Yalgin,
Bohdana Rovenko,
Ana Andjelković,
Margot Neefjes,
Burak Oymak,
Eric Dufour,
Ville Hietakangas,
Howard T. Jacobs
Affiliations
Cagri Yalgin
Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland; Institute of Biotechnology, FI-00014 University of Helsinki, Finland
Bohdana Rovenko
Institute of Biotechnology, FI-00014 University of Helsinki, Finland; Faculty of Biological and Environmental Sciences, FI-00014 University of Helsinki, Finland
Ana Andjelković
Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland
Margot Neefjes
Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland; Institute of Biotechnology, FI-00014 University of Helsinki, Finland
Burak Oymak
Institute of Biotechnology, FI-00014 University of Helsinki, Finland
Eric Dufour
Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland
Ville Hietakangas
Institute of Biotechnology, FI-00014 University of Helsinki, Finland; Faculty of Biological and Environmental Sciences, FI-00014 University of Helsinki, Finland
Howard T. Jacobs
Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland; Corresponding author
Summary: Dopaminergic (DA) neurons have been implicated as key targets in neurological disorders, notably those involving locomotor impairment, and are considered to be highly vulnerable to mitochondrial dysfunction, a common feature of such diseases. Here we investigated a Drosophila model of locomotor disorders in which functional impairment is brought about by pan-neuronal RNAi knockdown of subunit COX7A of cytochrome oxidase (COX). Despite minimal neuronal loss by apoptosis, the expression and activity of tyrosine hydroxylase was decreased by half. Surprisingly, COX7A knockdown specifically targeted to DA neurons did not produce locomotor defect. Instead, using various drivers, we found that COX7A knockdown in specific groups of cholinergic and glutamatergic neurons underlay the phenotype. Based on our main finding, the vulnerability of DA neurons to mitochondrial dysfunction as a cause of impaired locomotion in other organisms, including mammals, warrants detailed investigation.
