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

    Research output: Contribution to journalArticleScientificpeer-review

    3 Citations (Scopus)

    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.

    Original languageEnglish
    Article number101362
    JournalIscience
    Volume23
    Issue number8
    DOIs
    Publication statusPublished - 21 Aug 2020
    Publication typeA1 Journal article-refereed

    Keywords

    • Cell Biology
    • Molecular Biology
    • Neuroscience

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • General

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