Figure 3

Mutation of Parp rescues mitochondrial function in parkin mutants. (a) Increased levels of oxidative stress-related metabolites in parkin flies. The metabolites indicated in red are significantly upregulated. ND corresponds to a metabolite below detection threshold. The statistical significance for fold-changes was determined using Welch’s two-sample t-test (n=8). (b) Increased protein PARylation in parkin mutants is decreased upon a Parp mutation in parkin, Parp^CH1/+ double mutants. Whole-fly lysates were analysed using the indicated antibodies. Tubulin was used as a loading control. Three biological replicates are shown for each genotype. (c) Increased levels of NAD⁺ and NAD⁺ salvage metabolites and unchanged levels of oxidative stress marker methionine sulfoxide in parkin, Parp^CH1/+ double mutants. The metabolites indicated in red are significantly upregulated, as measured by metabolic profiling for the indicated comparisons of genotypes. Statistical significance was determined using Welch’s two-sample t-test (n=8). (d) Parp^CH1/+ mutation prevents the loss of Δψm in parkin mutants (mean±S.D.; asterisks, one-way ANOVA with Bonferroni’s multiple comparison test, n=5). (e) Parp^CH1/+ mutation increases respiration in parkin mutants (mean±S.D.; asterisks, one-way ANOVA with Bonferroni’s multiple comparison test). Genotypes: control: w¹¹¹⁸; parkin: park²⁵/park²⁵; parkin, parp^CH1/+: park²⁵, Parp^CH1/park²⁵