Figure 3.

Accumulation of misfolded proteins in mitochondrial phenocopies pink1 and parkin mutant flies. (a and b) Mitochondrial protein misfolding resulted in abnormal wing posture. (c and d) dOTC expression led to the formation of large mitochondrial clusters. Mitochondria were visualised by confocal analysis of the indirect flight muscles in mitochondria-targeted protein (mitoGFP) transgenic animals expressing either OTC or dOTC with da-GAL4 driver. Purple, nuclei; green, mitoGFP. (e–h) Ultrastructural defects in the indirect flight muscles of flies ubiquitously expressing dOTC. Tissues were analysed by transmission electron microscopy (TEM). mt, mitochondria. (i) Mitochondria-targeted protein misfolding caused motor impairment. Control, OTC and dOTC transgenic flies with 3- and 20-days-old were tested using a standard climbing assay (mean±S.D., n≥100 flies per genotype). Statistically significant values relative to control are indicated (two-way ANOVA with Bonferroni post test). (j) dOTC expression resulted in a reduction in total lifespan. Fly viability was scored over a period of 30 days, using a minimum of 200 flies per genotype. The viability of control, OTC and dOTC transgenic flies was compared. Statistical significance is indicated (log-rank, Mantel-Cox test)