Fig. 2: Genetic reduction of IS augments mitochondrial volume and function in dfmr1 mutant flies. | npj Metabolic Health and Disease

Fig. 2: Genetic reduction of IS augments mitochondrial volume and function in dfmr1 mutant flies.

From: PGC-1α integrates insulin signaling with mitochondrial physiology and behavior in a Drosophila model of Fragile X Syndrome

Fig. 2: Genetic reduction of IS augments mitochondrial volume and function in dfmr1 mutant flies.The alternative text for this image may have been generated using AI.

A–D Mitochondria in the insulin producing cells (IPCs) of the brain were labeled by expressing a genetically encoded UAS-mitoGFP construct in conjunction with the dilp2-Gal4 driver. A Two representative maximum-intensity projections of GFP-labeled mitochondria in the IPC processes of iso31Bw- wild type, dilp2/+ heterozygous mutant, dfmr1 homozygous mutant, and dilp2/+, dfmr1 double mutant flies. Scale bars: 5 μm. Images are oriented with the dorsal side on the left and the ventral side on the right. Sample number (N) per genotype = 8 brains. Brown-Forsythe and Welch ANOVA with Dunnet’s T3 multiple comparisons test revealed that genetic reduction of insulin signaling significantly improved (B) average mitochondrial length and (C) average volume per mitochondrion. D Total mitochondrial volume was not significantly increased in dilp2/+, dfmr1 double mutants, but showed a trend towards improvement (p = 0.084). Values represent mean ± SEM. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p < 0.0001. (E) Quantification of the NAD+/NADH ratio.. Each sample contained 10 fly bodies. Sample number (N) per genotype = 3. One-way ANOVAs revealed a significant group effect for the NAD+/NADH ratio (p = 0.0003). Post hoc Tukey tests indicated that while dfmr1 mutant flies had a significantly lower NAD+/NADH ratio than their iso31Bw- and dilp2/+ heterozygous mutant conspecifics, dilp2/+,dfmr1 double mutant flies had a significantly improved NAD+/NADH ratio. Values represent mean ± SEM. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. F Quantification of ATP levels relative to protein content. Each sample contained 5 fly bodies. Sample number (N) per genotype: iso31Bw- = 6, dilp2/+ = 5, dfmr1 = 6, dilp2/+, dfmr1 = 5. One-way ANOVAs revealed a significant group effect for ATP levels (p < 0.0001). Post hoc Tukey tests indicated that while dfmr1 mutant flies had a significantly lower ATP levels than their iso31Bw- and dilp2/+ mutant conspecifics, dilp2/+,dfmr1 double mutant flies had a significant boost in ATP levels. Values represent mean ± SEM. *p ≤ 0.05, ****p ≤ 0.0001.

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