A transporter essential for apical secretory organelles homeostasis in Toxoplasma gondii

Abstract

Apicomplexan parasites rely on the rhoptries and micronemes to coordinate egress, motility, and host cell invasion. In Toxoplasma gondii, mechanistic insights into the control of these organelles lipid composition remain sparse. Although nearly 60 T. gondii Major Facilitator Superfamily (MFS) are predicted, many remain functionally uncharacterized. The MFS protein HAP12 was previously annotated as an apicoplast protein contributing to invasion and organelle inheritance. Based on localization and phylogenetic analyses, we show that HAP12 (renamed TFP5), is predominantly associated with the Golgi, with additional signal in the ELC and apical compartments, without convincing evidence of a major apicoplast-associated pool. Furthermore, TFP5 clusters with a subgroup of MFS transporter facilitator proteins (TFPs) involved in the morphological integrity of secretory apical organelles. TFP5 depletion results in defective microneme secretion and pronounced alterations in rhoptry morphology and positioning. Structural analyses revealed that TFP5 is strongly similar to MFSD2-like lipid transporters, while lipidomic analyses showed substantial changes in parasite lipid composition following TFP5 depletion. Together, these findings support a model in which TFP5 regulates lipid homeostasis required for the function of apical secretory organelles, thereby critically contributing to parasite virulence.