The alternative oxidase AOX does not rescue the phenotype of tko25t mutant flies.
Bottom Line: AOX expression for 1 d after eclosion, or continuously throughout development, had no effect on the bang sensitivity of tko(25t) adults, and continued expression in adults older than 30 d also produced no amelioration of the phenotype.We conclude that AOX does not rescue tko(25t) and that the mutant phenotype is not solely due to limitations on electron flow in the respiratory chain, but rather to a more complex metabolic defect.The future therapeutic use of AOX in disorders of mitochondrial translation may thus be of limited value.
Affiliation: BioMediTech and Tampere University Hospital, FI-33014 University of Tampere, Tampere, Finland.Show MeSH
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Mentions: We confirmed the previous observation of decreased ATP levels in tko25t homozygotes compared with heterozygous controls (Figure 6A) but found no significant alteration thereof when either AOX or Ndi1 was expressed. Mitochondrial ROS production in tko25t homozygotes was also elevated in every case compared with heterozygous controls (Figure 6B). This was unaffected by expression of AOX but modestly alleviated by Ndi1 expression, despite the fact that the effect of Ndi1 on the overall organismal phenotype was deleterious. This, plus the wide variation in ROS production according to genetic background (reflecting different balancer chromosomes), implies that the tko25t organismal phenotype is also not directly determined by ROS.
Affiliation: BioMediTech and Tampere University Hospital, FI-33014 University of Tampere, Tampere, Finland.