Cardiomyocyte mitochondrial fragmentation parallels Drosophila cardiomyopathy induced by human Mfn2 mutants.

(A–C) Drosophila cardiomyocyte mitochondria visualized with tincΔ4-Gal4-driven mito-GFP in control (Gal4) and transgenic fly lines corresponding to those in Figure 5. Mitochondrial population size is quantified by measuring the diameter of individual mitochondria, presented in probability density curve (left graph), cumulative distribution curve (middle graph) and comparison of fragmented mitochondrial populations (right graph). Suppression of endogenous cardiomyocyte dMfn with the RNAi induces mitochondrial fragmentation, shown as smaller organelles and a leftward shift in the size distribution (A) Increased mitochondrial heterogeneity and/or fragmentation is seen with expression of wild-type or mutant human Mfn2 in the presence of endogenous dMfn (B). In dMfn-deficient heart tubes (C), wild-type human Mfn2 normalizes mitochondrial size, whereas mitochondrial fragmentation persists after Mfn2 M393I or R400Q replacement. Asterisk = p