TRYPANOSOMATIDAE PRODUCE ACETATE VIA A MITOCHONDRIAL ACETATE-SUCCINATE COA TRANSFERASE

Hydrogenosome-containing anaerobic protists, such as the trichomonads, produce large amounts of acetate by an acetate:succinate CoA transfer ase (ASCT)/succinyl CoA synthetase cycle. The notion that mitochondria and hydrogenosomes may have originated from the same alpha-proteobact erial endosymbiont has led us to look for the presence of a similar me tabolic pathway in trypanosomatids because these are the earliest-bran ching mitochondriate eukaryotes and because they also are known to pro duce acetate. The mechanism of acetate production in these organisms, however, has remained unknown. Four different members of the trypanoso matid family: promastigotes of leishmania mexicana mexicana, L. infant um and Phytomonas sp., and procyclics of Trypanosoma brucei were analy zed as well as the parasitic helminth Fasciola hepatica. They all use a mitochondrial ASCT for the production of acetate from acetyl CoA. Th e succinyl CoA that is produced during acetate formation by ASCT is re cycled presumably to succinate by a mitochondrial succinyl CoA synthet ase, concomitantly producing ATP from ADP. The ASCT of L. mexicana mex icana promastigotes was further characterized after partial purificati on of the enzyme. It has a high affinity for acetyl CoA (K-m 0.26 mM) and a low affinity for succinate (K-m 6.9 mM), which shows that signif icant acetate production can occur only when high mitochondrial succin ate concentrations prevail. This study identifies a metabolic pathway common to mitochondria and hydrogenosomes, which strongly supports a c ommon origin for these two organelles.