Year: 2026
Type: preprint
Abstract: 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. IMPORTANCE The Apicomplexa relies on tightly regulated secretion from specialized apical organelles for host cell invasion and intracellular proliferation, processes essential for pathogenicity. While the membrane trafficking pathways controlling these organelles are well characterized in Toxoplasma gondii , the contribution of membrane lipid transporters remains poorly understood. Here, we identify TFP5 as an Alveolata-conserved MFSD2-like transporter localized to the endomembrane system and micronemes. Consistent with a role in membrane lipid homeostasis, TFP5 depletion alters the parasite lipidome, severely impairs microneme secretion and rhoptry morphology, and consequently disrupts motility, egress, and host cell invasion without affecting intracellular replication. These findings reveal a critical role for membrane lipid homeostasis in the organization and function of apical secretory organelles and identify TFP5 as a potential therapeutic target against apicomplexan parasites.
Institution: University of Geneva
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G5051104502
OpenAlex ID: W7223885408