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

doi:10.1016/j.isci.2020.101362

Effects on Dopaminergic Neurons Are Secondary in COX-Deficient Locomotor Dysfunction in Drosophila

iScience. 2020 Aug 21;23(8):101362. doi: 10.1016/j.isci.2020.101362. Epub 2020 Jul 12.

Authors

Cagri Yalgin¹, Bohdana Rovenko², Ana Andjelković³, Margot Neefjes¹, Burak Oymak⁴, Eric Dufour³, Ville Hietakangas², Howard T Jacobs⁵

Affiliations

¹ Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland; Institute of Biotechnology, FI-00014 University of Helsinki, Finland.
² Institute of Biotechnology, FI-00014 University of Helsinki, Finland; Faculty of Biological and Environmental Sciences, FI-00014 University of Helsinki, Finland.
³ Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland.
⁴ Institute of Biotechnology, FI-00014 University of Helsinki, Finland.
⁵ Faculty of Medicine and Health Technology, FI-33014 Tampere University, Finland. Electronic address: howard.jacobs@tuni.fi.

Abstract

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.

Keywords: Cell Biology; Molecular Biology; Neuroscience.