Both human ferredoxins equally efficiently rescue ferredoxin deficiency in Trypanosoma brucei

0396398 - BC 2014 RIV GB eng J - Journal Article
Changmai, Piya - Horáková, Eva - Long, Shaojun - Černotíková, Eva - McDonald, Lindsay M. - Bontempi, Esteban J. - Lukeš, Julius
Both human ferredoxins equally efficiently rescue ferredoxin deficiency in Trypanosoma brucei.
Molecular Microbiology. Roč. 89, č. 1 (2013), s. 135-151. ISSN 0950-382X. E-ISSN 1365-2958
R&D Projects: GA ČR(CZ) GAP305/11/2179; GA MŠMT LH12104
Institutional support: RVO:60077344
Keywords : IRON-SULFUR CLUSTERS * CYTOCHROME-C-OXIDASE * BLOOD-STREAM FORM
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.026, year: 2013

Ferredoxins are highly conserved proteins that function universally as electron transporters. They not only require Fe-S clusters for their own activity, but are also involved in Fe-S formation itself. We identified two homologues of ferredoxin in the genome of the parasitic protist Trypanosoma brucei and named them TbFdxA and TbFdxB. TbFdxA protein, which is homologous to other eukaryotic mitochondrial ferredoxins, is essential in both the procyclic (=insect-transmitted) and bloodstream (mammalian) stage, but is more abundant in the active mitochondrion of the former stage. Depletion of TbFdxA caused disruption of Fe-S cluster biogenesis and lowered the level of intracellular haem. However, TbFdxB, which is present exclusively within kinetoplastid flagellates, was non-essential for the procyclic stage, and double knock-down with TbFdxA showed this was not due to functional redundancy between the two homologues. Heterologous expressions of human orthologues HsFdx1 and HsFdx2 fully rescued the growth and Fe-S-dependent enzymatic activities of TbFdxA knock-down. In both cases, the genuine human import signals allowed efficient import into the T.brucei mitochondrion. Given the huge evolutionary distance between trypanosomes and humans, ferredoxins clearly have ancestral and highly conserved function in eukaryotes and both human orthologues have retained the capacity to participate in Fe-S cluster assembly.
Permanent Link: http://hdl.handle.net/11104/0224188