The ATP synthase of Trypanosoma brucei is developmentally regulated by an inhibitor peptide.

The Trypanosoma brucei ATP synthase, like those of other organisms, is composed of two moieties, the membrane bound F0 and the catalytic F1 with each of these parts comprised of multiple subunits. In addition, an endogenous inhibitor peptide of the ATP synthase has been identified from a variety of sources. Previous reports have suggested that the Trypanosoma brucei ATPase may not possess such an inhibitor. Recently, we have isolated an inhibitor peptide fraction from the procyclic form of Trypanosoma brucei by modification of a previously published procedure. This fraction is composed of two dominant polypeptides with estimated molecular weights of 14,000 and 12,000 and an additional polypeptide of 15,000 that may or may not be functionally required. Antibodies raised to the smallest polypeptide showed strong cross reactivity with the other two polypeptides, suggesting that they are related. Antibodies to rat liver inhibitor peptide show cross reactivity with the same polypeptides in crude fractions. The inhibitor peptide fraction strongly suppresses the ATPase activity of membrane bound ATPase in a Mg(2+)-dependent manner and is cold and heat stable. Using antibodies to the smallest polypeptide and rat liver inhibitor peptide we have shown in crude extracts from the three experimental life cycle stages of T. brucei that the inhibitor peptide(s) is developmentally regulated to a modest extent. The pattern of regulation is opposite of the pattern seen for the ATP synthase complex. This suggests that the ATP synthase is stringently controlled in T. brucei in a unique way.