Figure 4.

ATP5F1D p.Pro82Leu and p.Val106Gly Are Partial Loss-of-Function Variants

(A) The observed/expected ratio of flies shows the rescue of lethality by the human genes including both variants in the Drosophila null background.

(B and C) Expression of ATPsynδ RNAi by ey-Gal4 caused pupal lethality and an extremely reduced head size (ey-Gal4/UAS-ATPsynδ RNAi; UAS-LacZ/+) (C), whereas control animals without the ey-Gal4 driver (UAS-ATPsynδ RNAi/+; UAS-LacZ) showed normal head development (B).

(D–F) Light micrographs of fly eyes expressing ey-Gal4 and ATPsynδ RNAi together with UAS-ATP5F1D^WT (D), UAS-ATP5F1D^P82L (E), or UAS-ATP5F1D^V106G (F). We found that expression of ATP5F1D^WT rescued the tiny-head phenotype caused by knockdown of ATPsynδ (D). However, a portion of adult flies expressing ATPsynδ RNAi together with ATP5F1D^P82L or ATP5F1D^V106G exhibited abnormal eye morphology, including glassy eyes, small eyes, and bar eyes (E and F). Quantification of the phenotypes shows that expression of ATP5F1D^V106G causes more severe defects than ATP5F1D^P82L (J).

(G–I) Light micrographs of fly antenna expressing ey-Gal4 and ATPsynδ RNAi together with UAS-ATP5F1D^WT (G), UAS-ATP5F1D^P82L (H), or UAS-ATP5F1D^V106G (I).

(K) Quantification of the antenna morphology phenotypes described in (G)–(I).