Evidence that transport of iron from the lysosome to the cytosol in African trypanosomes is mediated by a mucolipin orthologue.

摘要: Bloodstream-form Trypanosoma brucei acquire iron by receptor-mediated endocytosis of host transferrin. However, the mechanism(s) which is then transferred from lysosome to cytosol are unresolved. Here, we provide evidence for involvement a protein (TbMLP) orthologous mammalian endolysosomal cation channel Mucolipin 1. In T.brucei, show that this localized single parasite lysosome. TbMLP null mutants could only be generated in presence an expressed ectopic copy, suggesting essential. RNAi-mediated ablation resulted growth defect vitro and led sevenfold increase susceptibility iron-chelators deferoxamine salicylhydroxamic acid. Conditional remained viable when copy was repressed, but were hypersensitive displayed similar observed following RNAi. The conditional nulls also retained virulence vivo absence doxycycline inducer. These data strong has role import into African trypanosomes. They indicate even expression greatly reduced, there sufficient protein, or alternative mechanism, with adequate supply cytosolic iron.