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

Cell Metab. 2009 May;9(5):449-60. doi: 10.1016/j.cmet.2009.03.004.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimycin A / analogs & derivatives
  • Antimycin A / pharmacology
  • Ciona intestinalis / enzymology
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Knockdown Techniques
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / enzymology*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Oxidative Phosphorylation*
  • Oxidoreductases / biosynthesis*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Phenotype
  • Plant Proteins
  • Potassium Cyanide / pharmacology
  • Protein Deglycase DJ-1
  • Reactive Oxygen Species / metabolism


  • Drosophila Proteins
  • Enzyme Inhibitors
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • Plant Proteins
  • Reactive Oxygen Species
  • Surf-1 protein
  • antimycin
  • Antimycin A
  • Oxidoreductases
  • alternative oxidase
  • CYPE protein, Drosophila
  • Electron Transport Complex IV
  • DJ-1beta protein, Drosophila
  • Protein Deglycase DJ-1
  • Potassium Cyanide