The ferredoxin redox system – an essential electron distributing hub in the apicoplast of Apicomplexa.

The apicoplast, a relict plastid found in most species of the phylum Apicomplexa, harbors the ferredoxin redox system which supplies electrons to enzymes of various metabolic pathways in this organelle. Recent reports in Toxoplasma gondii and Plasmodium falciparum have shown that the iron-sulfur cluster (FeS)-containing ferredoxin is essential in tachyzoite and blood-stage parasites, respectively. Here we review ferredoxin's crucial contribution to isoprenoid and lipoate biosynthesis as well as tRNA modification in the apicoplast, highlighting similarities and differences between the two species. We also discuss ferredoxin's potential role in the initial reductive steps required for FeS synthesis as well as recent evidence that offers an explanation for how NADPH required by the redox system might be generated in Plasmodium spp. Plant-type ferredoxin in the apicoplast provides electrons derived from NADPH to several enzymes, all of which are iron-sulfur cluster-containing proteins. Deletion of ferredoxin in Plasmodium falciparum blood-stage parasites or Toxoplasma gondii tachyzoites is lethal. Methylerythritol phosphate (MEP) isoprenoid precursor biosynthesis may be the most important ferredoxin-dependent pathway. Lipoate synthesis, important for functional fatty acid synthesis in the apicoplast, and isoprenoid-dependent transfer RNA (tRNA) modification, also rely on ferredoxin. Ferredoxin could be required for the biosynthesis of iron-sulfur cluster-containing proteins via the sulfur utilization factor (SUF) system in the apicoplast, but experimental evidence for this activity is still needed. The source of NADPH, a prerequisite for the functioning of the ferredoxin redox system, is still a matter of debate [ABSTRACT FROM AUTHOR]