The F1-ATP synthase complex in bloodstream stage trypanosomes has an unusual and essential function.
Survival of bloodstream form Trypanosoma brucei, the agent of African sleeping sickness, normally requires mitochondrial gene expression, despite the absence of oxidative phosphorylation in this stage of the parasite's life cycle. Here we report that silencing expression of the alpha subunit of the mitochondrial F(1)-ATP synthase complex is lethal for bloodstream stage T. brucei as well as for T. evansi, a closely related species that lacks mitochondrial protein coding genes (i.e. is dyskinetoplastic). Our results suggest that the lethal effect is due to collapse of the mitochondrial membrane potential, which is required for mitochondrial function and biogenesis. We also identified a mutation in the gamma subunit of F(1) that is likely to be involved in circumventing the requirement for mitochondrial gene expression in another dyskinetoplastic form. Our data reveal that the mitochondrial ATP synthase complex functions in the bloodstream stage opposite to that in the insect stage and in most other eukaryotes, namely using ATP hydrolysis to generate the mitochondrial membrane potential.
Schnaufer
Achim
A
Seattle Biomedical Research Institute, Seattle, WA 98109-5219, USA. achim.schnaufer@sbri.org
Clark-Walker
G Desmond
GD
Steinberg
Alodie G
AG
Stuart
Ken
K
D000818:Animals; D008564:Membrane Potentials / Q000502:physiology; D051336:Mitochondrial Membranes / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D019761:Phosphorus-Oxygen Lyases / Q000037:antagonists & inhibitors; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors; D017393:RNA Editing / Q000502:physiology; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000254:growth & development*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism
D015800:Protozoan Proteins; C418993:TbMP52 protein, Trypanosoma brucei; D014643:Variant Surface Glycoproteins, Trypanosoma; D025261:Mitochondrial Proton-Translocating ATPases; D019761:Phosphorus-Oxygen Lyases