Iron-induced changes in pyruvate metabolism of Tritrichomonas foetus and involvement of iron in expression of hydrogenosomal proteins

The main function of the hydrogenosome, a typical organelle of trichomonads , is to convert malate or pyruvate to H-2, CO2 and acetate by a pathway ass ociated with ATP synthesis. This pathway relies on activity of iron-sulfur proteins such as pyruvate:ferredoxin oxidoreductase (PFOR), hydrogenase and ferredoxin. To examine the effect of iron availability on proper hydrogeno somal function, the metabolic activity of the hydrogenosome and expression of hydrogenosomal enzymes were compared in Tritrichomonas foetus maintained under iron-rich (150 muM iron nitrilotriacetate) or iron-restricted (180 m uM 2,2-dipyridyl) conditions in vitro. The activities of PFOR and hydrogena se, and also production of acetate and H-2, were markedly decreased or abse nt in iron-restricted trichomonads. Moreover a decrease in activity of the hydrogenosomal malic enzyme, which is a non-Fe-S protein, was also observed . Impaired function of hydrogenosomes under iron-restricted conditions was compensated for by activation of the cytosolic pathway, mediating conversio n of pyruvate to ethanol via acetaldehyde. This metabolic switch was fully reversible. Production of hydrogen by iron-restricted trichomonads was rest ored to the level of organisms grown under iron-rich conditions within 3 h after addition of 150 muM iron nitrilotriacetate. Protein analysis of purif ied hydrogenosomes from iron-restricted cells showed decreased levels of pr oteins corresponding to PFOR, malic enzyme and ferredoxin. Accordingly, the se cells displayed decreased steady-state level and synthesis of mRNAs enco ding PFOR and hydrogenosomal malic enzyme. These data demonstrate that iron is essential for function of the hydrogenosome, show its involvement in th e expression of hydrogenosomal proteins and indicate the presence of iron-d ependent control of gene transcription in Tf. foetus.