Figure 4.

Inhibition of mitochondrial fission has detrimental effects in C. elegans models of Huntington’s disease expressing expanded polyglutamine tracts in body wall muscle. To examine the effect of disrupting mitochondrial fission in worm models of HD, a body wall muscle (BW-Htt74Q worms) model of HD was crossed to a drp-1 deletion mutant. The drp-1 mutation significantly decreased movement (A) and lifespan (B) in BW-Htt74Q worms but had no effect on wild-type worms (A, C). Loss of drp-1 resulted in decreased fertility (D) and slower post-embryonic development (E) in both BW-Htt74Q and wild-type worms. While the drp-1 deletion did not affect oxygen consumption (F) in either genotype, it resulted in a decreased levels of ATP (G). Deletion of drp-1 did not decrease the mitochondrial fragmentation that is present in BW-Htt74Q worms (H), as indicated by quantification of mitochondrial number (I), mitochondrial area (J) and mitochondrial shape (K). Note that we used wild-type worms as a control instead of BW-Htt28Q worms because we observed the formation of aggregates in BW-Htt28Q worms, which could complicate the interpretation of the results. The images in panel H are compressed z-stacks collected on a confocal microscope. Scale bars indicate 10 µM. A minimum of three biological replicates were performed. Bars indicate the mean value. One-way ANOVA was used to assess significance in H, I and J. Two-way ANOVA was used to assess significance in A, C, E, and F. Log-rank test was used to assess significance in B. Repeated measures ANOVA was used to assess significance in D. Error bars indicate SEM. ROI - region of interest. *p<0.05, **p<0.01, ***p<0.001.