Fig 14. Hypothetical model for ion homeostasis and osmoregulation in Toxoplasma.

Na⁺ homeostasis in Toxoplasma is accomplished via cooperation between ATP4, TgNHE1 and TgPiT. When intake of Na⁺ is reduced through TgPiT ablation, compensatory mechanisms may include decreased activity of ATP4 (dashed arrows) and increased activity of TgNHE1 (thick arrows), both resulting in reduced H⁺ concentrations in the parasite and thus cytosolic alkalinization. Consequently, the mutant decreases the export of H⁺ mediated by V-H⁺-ATPase (dashed lines). ΔTgPiT parasites have a severe constitutive loss in cytosolic ionic strength through reduced internalization of P_i and sodium into the parasite and impaired expulsion of these ions from VAC into the cytosol. Due to low P_i availability, the mutant has reduced concentrations of total P_i and polyP that is compensated for increased numbers of acidocalcisomes in an attempt to garner as much phosphate as possible.