@article{1bbfd65fc2674341b17c3a7515e3e930,
title = "Effects on Dopaminergic Neurons Are Secondary in COX-Deficient Locomotor Dysfunction in Drosophila",
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",
author = "Cagri Yalgin and Bohdana Rovenko and Ana Andjelkovi{\'c} and Margot Neefjes and Burak Oymak and Eric Dufour and Ville Hietakangas and Jacobs, \{Howard T.\}",
note = "Funding Information: We thank Serge Birman for the supply of the TH-GAL4 line; Hermann Aberle for providing the anti-VGlut antibody; Mikko Airavaara, Kira Holmstr?m, Marten Szibor, Ying Liu, Tapio Heino, and Moussa Youdim for advice and fruitful discussions; Tea Tuomela, Eveliina Teeri, Anna Kuukasj?rvi, and Lyon Bruinsma for technical assistance; Troy Faithfull for critical reading of the manuscript; and University of Helsinki LMU core facility for providing facilities for imaging. This work was supported by the Academy of Finland (Centre of Excellence grant 272376; Academy Professorship grant 283157 to H.T.J.; Centre of Excellence in Stem Cell Metabolism grant 312439 to V.H.); the French Muscular Dystrophy Association (AFM-T?l?thon), grant no.19981 to C.Y.), the Finnish Cultural Foundation (grant 00181201 to C.Y. and 00160101 to A.A.), the Scientific Research Projects Coordination Unit of Pamukkale University (grant no. 2018TIPF034 to B.O.), Tampere University, and the Sigrid Jus?lius Foundation. The work used the facilities of the Light Microscopy Unit (LMU, Institute of Biotechnology, University of Helsinki) and services for Drosophila maintenance and culture (Tampere Drosophila Facility and the Helsinki Drosophila core facility, Hi-Fly) all of which are supported by funding from Biocenter Finland. Conceptualization, C.Y. and H.T.J.; Methodology, C.Y. E.D. and H.T.J.; Investigation, C.Y. B.R. A.A. M.N. B.O. and E.D.; Writing ? Original Draft, H.T.J. and C.Y.; Writing ? Review \& Editing, all authors; Visualization, H.T.J. and C.Y.; Funding Acquisition, H.T.J. and V.H.; Supervision, H.T.J. C.Y. E.D. and V.H. The authors declare no competing interests. Funding Information: We thank Serge Birman for the supply of the TH-GAL4 line; Hermann Aberle for providing the anti-VGlut antibody; Mikko Airavaara, Kira Holmstr{\"o}m, Marten Szibor, Ying Liu, Tapio Heino, and Moussa Youdim for advice and fruitful discussions; Tea Tuomela, Eveliina Teeri, Anna Kuukasj{\"a}rvi, and Lyon Bruinsma for technical assistance; Troy Faithfull for critical reading of the manuscript; and University of Helsinki LMU core facility for providing facilities for imaging. This work was supported by the Academy of Finland (Centre of Excellence grant 272376 ; Academy Professorship grant 283157 to H.T.J.; Centre of Excellence in Stem Cell Metabolism grant 312439 to V.H.); the French Muscular Dystrophy Association ( AFM-T{\'e}l{\'e}thon ), grant no. 19981 to C.Y.), the Finnish Cultural Foundation (grant 00181201 to C.Y. and 00160101 to A.A.), the Scientific Research Projects Coordination Unit of Pamukkale University (grant no. 2018TIPF034 to B.O.), Tampere University , and the Sigrid Jus{\'e}lius Foundation . The work used the facilities of the Light Microscopy Unit (LMU, Institute of Biotechnology, University of Helsinki) and services for Drosophila maintenance and culture (Tampere Drosophila Facility and the Helsinki Drosophila core facility, Hi-Fly) all of which are supported by funding from Biocenter Finland . Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = aug,
day = "21",
doi = "10.1016/j.isci.2020.101362",
language = "English",
volume = "23",
number = "8",
}