Expression of Nf1hs.PT greatly increases the resistance to paraquat-induced oxidative stress, compared to wild-type.
Expression of Nf1hs.PT in a wild-type background increases aconitase activity by more than 90%.
Upregulation of Nf1hs.PT expression by maintaining these flies at 25[o]C throughout life results in an increase in mean life span of 49% for male flies and 68% for females and an increase in maximum life span of 38% for males and 52% for females. By contrast, when Nf1hs.PT flies are maintained at 25[o]C through embryogenesis and 4 days in adulthood but then switched to 18[o]C for the remainder of their adult life, results in the elimination of the extension of maximum life span and a reduction in the extension of mean life span. The mortality rates of these flies do not change compared to wild-type.
Both fertility and fecundity are higher in Nf1hs.PT-expressing flies compared to wild-type. This is not because the Nf1hs.PT flies are bigger, as they have similar body lengths to controls, although Nf1hs.PT females are slightly heavier.
Testing the stress resistance of Nf1hs.PT-overexpressing flies by assessing up-climbing ability reveals that these flies are highly resistant to heat stress and paraquat-induced oxidative stress, with Nf1hs.PT females showing a 56% increase in survival time and the males a 51% increase in survival time during paraquat exposure, relative to controls. However Nf1hs.PT flies are not more resistant to desiccation.
Mitochondria NADH-linked (pyruvate+malate) respiration rates from Nf1hs.PT overexpressing flies are 25%-38% higher than those of controls, in the presence of ADP, but not in the absence of ADP. Consequently, the respiratory control ratio is significantly higher for these mitochondria than for controls. Nf1hs.PT-overexpressing mitochondria have a 54% higher ATP production rate when metabolising NADH-linked substrates, compared to controls. In contrast, the respiration rates recorded when using the FADH[]-linked complex II substrate succinate are essentially the same as in controls, with or without ADP.
Complex I activity is 28% higher in Nf1hs.PT-expressing flies compared to controls.
Mitochondrial H[]O[] production is reduced by 58-59% in Nf1hs.PT mutants compared to control flies. This reduced mitochondrial ROS is also associated with increased mitochondrial aconitase activity throughout life.
Expression of Nf1hs.PT in a wild-type background using heat shock has no effect on learning scores.