Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex

Trichomonas vaginalis is a unicellular microaerophilic eukaryote that lacks mitochondria yet contains an alternative organelle, the hydrogenosome, involved in pyruvate metabolism. Pathways between the two organelles differ substantially: in hydrogenosomes, pyruvate oxidation is catalysed by pyruvate:ferredoxin oxidoreductase (PFOR), with electrons donated to an [Fe]-hydrogenase which produces hydrogen. ATP is generated exclusively by substrate-level phosphorylation in hydrogenosomes, as opposed to oxidative phosphorylation in mitochondria 1 . PFOR and hydrogenase are found in eubacteria and amitochondriate eukaryotes, but not in typical mitochondria 2 , 3 , 4 . Analyses of mitochondrial genomes indicate that mitochondria have a single endosymbiotic origin from an α-proteobacterial-type progenitor 5 . The absence of a genome in trichomonad hydrogenosomes 6 precludes such comparisons, leaving the endosymbiotic history of this organelle unclear 7 . Although phylogenetic reconstructions of a few proteins indicate that trichomonad hydrogenosomes share a common origin with mitochondria 8 , 9 , 10 , 11 , others do not 2 , 3 , 4 , 7 . Here we describe a novel NADH dehydrogenase module of respiratory complex I that is coupled to the central hydrogenosomal fermentative pathway to form a hydrogenosomal oxidoreductase complex that seems to function independently of quinones. Phylogenetic analyses of hydrogenosomal complex I-like proteins Ndh51 and Ndh24 reveal that neither has a common origin with mitochondrial homologues. These studies argue against a vertical origin of trichomonad hydrogenosomes from the proto-mitochondrial endosymbiont.