Which is a phenotype associated with mutations in ATP synthase? Figure 1.jpg longer than normal lifespan sterility increased locomotor activity, especially as aging progresses faster than normal larval and pupal development
Here we utilize a novel, well-characterized, endogenous mitochondrial mutation in the ATP6 gene of Drosophila melanogaster with a nearly complete loss of ATP synthase activity. These Drosophila mutants have a missense mutation in ATP6 (G to A transition resulting in a glycine to glutamate change at position 116 in the protein), the mitochondrial gene encoding subunit 6 of the F1Fo-ATP synthase(complex V of the respiratory chain. ATP6 allows for the hydrogen ion translocation required for the rotation of the Fo motor and the production of ATP from ADP. Drosophila ATP61 mutants model human mitochondrial encephalomyopathy and demonstrate
ATP61 Drosophila mutants exhibit a stereotyped phenotypic progression that is analogous to the symptomatic progression reported for many human mitochondrial disease patients. ATP61 mutant flies demonstrate stress sensitivity, shortened lifespan, muscle degeneration and abnormal mitochondrial morphology. ATP61 animals come out of the pupal case looking and acting completely normal and are morphologically and behaviorally indistinguishable from wildtype animals. ATP61 animals exhibit a stereotypical progression of disease following onset (~day 8) when the animals begin to have reduced locomotor activity. By day 13, ATP61 animals are sensitive to mechanical stress resulting in paralysis, suggesting neuromuscular impairment. At ~day 20, ATP61 animals can be observed having sporadic and unprovoked seizure-like activity. Late in pathogenesis ATP61 phenotypes continue to worsen until their premature death.
We discovered that ATP61 animals have a similar developmental survival rate as wildtype animals whether they are raised at 22°C or 29°C (Figure 1C). Interestingly, ATP61 animals show a modest but significant shortening in the time of development during the larval and pupal stages at 22°C and during the larval stage at 29°C (Figure 1D). Additionally, ATP61 females lay significantly more eggs than wildtype animals during their first week of life (Figure 1E). These data demonstrate that the altered physiology of ATP61 animals results in an accelerated development and increase in female fecundity. Such effects could cause increase utilization of energy early in life to ensure survival despite the dramatically altered physiology.
To examine the seizure behavior we asked whether sensory hyperstimulation, such as a strobe light, could elicit seizure behavior in ATP61 flies. Video analysis of locomotor function prior to, during, and following 1450 fpm (flashes per minute) strobelighting (20 seconds) was used to examine the ability to induce seizure behavior by sensory hyperstimulation alone. Although strobe lighting did not affect the locomotion of wildtype flies, ATP61 animals exhibited convulsive behavior with a high penetrance both during and after the strobe light. Surprisingly, the convulsive behavior was followed by full paralysis that continued well after resumption of normal lighting (Figure 1F). This phenotype was also progressive, as young animals did not exhibit convulsions or paralysis (Figure 1F).
Which is a phenotype associated with mutations in ATP synthase?
Figure 1.jpg
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longer than normal lifespan |
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sterility |
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increased locomotor activity, especially as aging progresses |
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faster than normal larval and pupal development |
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