Expression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila complements defects in mitochondrial oxidative phosphorylation.

TitleExpression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila complements defects in mitochondrial oxidative phosphorylation.
Publication TypeJournal Article
Year of Publication2009
AuthorsFernandez-Ayala, DJM, Sanz, A, Vartiainen, S, Kemppainen, KK, Babusiak, M, Mustalahti, E, Costa, R, Tuomela, T, Zeviani, M, Chung, J, O'Dell, KMC, Rustin, P, Jacobs, HT
JournalCell Metab
Volume9
Issue5
Pagination449-60
Date Published2009 May
ISSN1932-7420
KeywordsAnimals, Antimycin A, Ciona intestinalis, Drosophila, Drosophila Proteins, Electron Transport Complex IV, Enzyme Inhibitors, Gene Knockdown Techniques, Membrane Proteins, Mitochondria, Mitochondrial Proteins, Nerve Tissue Proteins, Oxidative Phosphorylation, Oxidoreductases, Phenotype, Plant Proteins, Potassium Cyanide, Reactive Oxygen Species
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-1beta, 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.

DOI10.1016/j.cmet.2009.03.004
Alternate JournalCell Metab.
Citation Key10.1016/j.cmet.2009.03.004
PubMed ID19416715
Grant ListGGP07019 / / Telethon / Italy