A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

作者:Slavic Ksenija; Krishna Sanjeev; Lahree Aparajita; Bouyer Guillaume; Hanson Kirsten K; Vera Iset; Pittman Jon K; Staines Henry M*; Mota Maria M*
来源:Nature Communications, 2016, 7(1): 10403.
DOI:10.1038/ncomms10403

摘要

Iron is an essential micronutrient but is also highly toxic. In yeast and plant cells, a key detoxifying mechanism involves iron sequestration into intracellular storage compartments, mediated by members of the vacuolar iron-transporter (VIT) family of proteins. Here we study the VIT homologue from the malaria parasites Plasmodium falciparum (PfVIT) and Plasmodium berghei (PbVIT). PfVIT-mediated iron transport in a yeast heterologous expression system is saturable (K-m similar to 14.7 mu M), and selective for Fe2+ over other divalent cations. PbVIT-deficient P. berghei lines (Pbvit(-)) show a reduction in parasite load in both liver and blood stages of infection in mice. Moreover, Pbvit(-) parasites have higher levels of labile iron in blood stages and are more sensitive to increased iron levels in liver stages, when compared with wild-type parasites. Our data are consistent with Plasmodium VITs playing a major role in iron detoxification and, thus, normal development of malaria parasites in their mammalian host.

  • 出版日期2016-1