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Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency

Citation

Mercer, SW and La Fontaine, S and Warr, C and Burke, R, Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency, Journal of Neurochemistry, 137, (3) pp. 360-370. ISSN 0022-3042 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 International Society for Neurochemistry

DOI: doi:10.1111/jnc.13567

Abstract

Glutathione (GSH) is a tripeptide often considered to be the master antioxidant in cells. GSH plays an integral role in cellular redox regulation and is also known to have a role in mammalian copper homeostasis. In vitro evidence suggests that GSH is involved in copper uptake, sequestration and efflux. This study was undertaken to further investigate the roles that GSH plays in neuronal copper homeostasis in vivo, using the model organism Drosophila melanogaster. RNA interference-mediated knockdown of the Glutamate-cysteine ligase catalytic subunit gene (Gclc) that encodes the rate-limiting enzyme in GSH biosynthesis was utilised to genetically deplete GSH levels. When Gclc was knocked down in all neurons, this caused lethality, which was partially rescued by copper supplementation and was exacerbated by additional knockdown of the copper uptake transporter Ctr1A, or over-expression of the copper efflux transporter ATP7. Furthermore, when Gclc was knocked down in a subset of neuropeptide-producing cells, this resulted in adult progeny with unexpanded wings, a phenotype previously associated with copper dyshomeostasis. In these cells, Gclc suppression caused a decrease in axon branching, a phenotype further enhanced by ATP7 over-expression. Therefore, we conclude that GSH may play an important role in regulating neuronal copper levels and that reduction in GSH may lead to functional copper deficiency in neurons in vivo. © 2016 International Society for Neurochemistry.

Item Details

Item Type:Refereed Article
Keywords:ATP7; copper; CTR1; Drosophila; glutamate-cysteine ligase; glutathione; copper; glutamate cysteine ligase; glutathione; Menkes protein; ATP7 protein, Drosophila; calcitonin; cation transport protein; copper; Ctr1A protein, Drosophila; glutathione
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Warr, C (Professor Coral Warr)
ID Code:131332
Year Published:2016
Web of Science® Times Cited:12
Deposited By:Medicine
Deposited On:2019-03-13
Last Modified:2019-04-26
Downloads:0

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