ETFDH is required for RQ-dependent metabolism.

(a) Schematic showing role of QDHs in the electron transport chain in UQ and RQ-dependent metabolism. (b) Requirement for QDHs in RQ-dependent metabolism. RNAi knockdown of QDH genes was performed by feeding dsRNA-expressing bacterial strains to L1 worms until they developed to fertile adults. Their L1 progeny were subjected to 15 h of 200 μM KCN treatment followed by a 3 h recovery (see Materials and methods). An RNAi clone targeting GFP was used as a negative control. Data show movement scores after 3 h recovery and represent biological replicates, with 2–3 technical replicates in each. (c) Conserved divergent residues from host (blue), C. elegans (yellow), parasite (red) and mollusk/annelids (green) were identified using S3Det [38] with a cutoff of 2 (see Materials and methods). Residues are numbered according to C. elegans. Phe437 (arrow) is conserved in RQ-containing species but is not present in hosts. (d) Crystal structure of porcine ETFDH (PDB: 2GMH) in complex with UQ5 (orange) as visualized in Chimera [85] with C. elegans sequence (pink residues) and H. sapiens sequence (cyan residues) threaded over by homology (residues from (c) circled in red). The Phe437Cys residue (green) is located near the quinone binding site [89] where both RQ and UQ must be able to bind in C. elegans and parasites.