The role of subunit 9 in the structure, function and regulation of the Trypanosoma brucei ATP synthase

The Trypanosoma brucei ATP synthase functions as a hydrolase in bloodstream form parasites and as a synthase in the procyclic form parasites. The dual functionality of the complex enables the parasite to maintain the membrane potential in both environments. This study focuses on the role of the F0 component subunit 9 in the structure, function and regulation of the ATP synthase. We have shown that the T. brucei produces two isoforms of S9 (S9-1 and S9-2). Each isoform is differentially regulated. Both isoforms are incorporated into the ATP synthase, within the same F0 component. Expression of each isoform was decreased by RNA interference, however, S9-2 increased initially in response to RNAi before ultimately decreasing. Loss of S9 results in a loss in the ATP synthase complex and, interestingly, a loss in the complexes of the electron transport chain. This results in an unexpected loss of membrane potential in the procyclic cells. Loss of S9 also results in a decrease in the alpha and beta subunits expression at the transcript and protein levels. This suggests that S9 plays a major role in the regulation of the ATP synthase and other mitochondrial complexes.