Orchestrating a heist: uptake and storage of metals by apicomplexan parasites

Abstract

The acquisition and storage of metals has been a preoccupation of life for millennia. Transition metals, in particular iron, copper and zinc, have vital roles within cells. However, metals also make dangerous cargos; inappropriate uptake or storage of transition metals leads to cell death. This paradox has led to cells developing elegant and frequently redundant mechanisms for fine-tuning local metal concentrations. In the context of infection, pathogens must overcome further hurdles, as hosts act to weaponize metal availability to prevent pathogen colonization and spread. Here, we detail the methods used by the Apicomplexa, a large family of eukaryotic parasites, to obtain and store essential metals.

Figure 1. Summary of expected iron, zinc and copper transporters in apicomplexan parasites

A schematic showing the major organelles of T. gondii as a model apicomplexan and the expected localisation of transporters involved in metal transport throughout the cell. As the parasitophorous vacuolar membrane (PVM) is permeable, it is not known if transporters would be required to move metals into the PV space. Apicomplexa appear to be able to endocytose material from the host which may provide a source of metal-containing proteins Iron is required in the mitochondria and apicoplast (see text for details) and may be required in the ER and is likely stored in a vacuolar compartment (VAC). A single apicoplast-localised transporter has been indicated, but it is likely that more than one are required to cross the four membranes of the apicoplast. Zinc is likely required in the mitochondria, ER and Golgi and a zinc transporter has been localised multiple compartments, potentially acidocalcisomes and the vacuolar compartment. Copper is required in the mitochondria and copper transporters have been putatively localised to the VAC and Golgi. Transparent transporters (marked with ?) show the likely location of transporters that have not yet been identified. Iron/iron transporters- red, copper/copper transporters-blue and zinc/zinc transporters - grey.