Expression of the ciona intestinalis alternative oxidase (aox) in drosophila complements defects in mitochondrial oxidative phosphorylation

Fernandez-Ayala, D.J.M. et al. (2009) Expression of the ciona intestinalis alternative oxidase (aox) in drosophila complements defects in mitochondrial oxidative phosphorylation. Cell Metabolism, 9(5), pp. 449-460. (doi: 10.1016/j.cmet.2009.03.004)

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Abstract

Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders. The single-subunit alternative oxidase (AOX) found in many eukaryotes, but not in arthropods or vertebrates, offers a potential bypass of the OXPHOS cytochrome chain under conditions of pathological OXPHOS inhibition. We have engineered Ciona intestinalis AOX for conditional expression in Drosophila melanogaster. Ubiquitous AOX expression produced no detrimental phenotype in wild-type flies. However, mitochondrial suspensions from AOX-expressing flies exhibited a significant cyanide-resistant substrate oxidation, and the flies were partially resistant to both cyanide and antimycin. AOX expression was able to complement the semilethality of partial knockdown of both cyclope (COXVIc) and the complex IV assembly factor Surf1. It also rescued the locomotor defect and excess mitochondrial ROS production of flies mutated in dj-1[beta], a Drosophila homolog of the human Parkinson's disease gene DJ1. AOX appears to offer promise as a wide-spectrum therapeutic tool in OXPHOS disorders.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sanz Montero, Professor Alberto and O'Dell, Professor Kevin
Authors: Fernandez-Ayala, D.J.M., Sanz., A., Vartiainen, S., Kemppainen, K.K., Babusiak, M., Mustalahti, E., Costa, R., Tuomela, T., Zeviani, M., Chung, J., O'Dell, K.M.C., Rustin, P., and Jacobs, H.T.
Subjects:Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Cell Metabolism
ISSN:1550-4131
ISSN (Online):1932-7420
Published Online:05 May 2009

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