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)
Full text not currently available from Enlighten.
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: | O'Dell, Professor Kevin and Sanz Montero, Professor Alberto |
| 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 College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Cell Metabolism |
| ISSN: | 1550-4131 |
| ISSN (Online): | 1932-7420 |
| Published Online: | 05 May 2009 |
University Staff: Request a correction | Enlighten Editors: Update this record
Deposit and Record Details
Deposit and Record Details