Toxoplasma gondii GRA25 alters the morphology of the parasitophorous vacuole membrane communicating with host mitochondria

Abstract

Abstract Mitochondria participate in a wide range of cellular processes, from energy metabolism to host defense. Some infectious microbes alter their host environments by accessing/altering mitochondrial functions. The intracellular parasite Toxoplasma gondii sequestrates host mitochondria, in part by nutrient uptake. Here we show that the T. gondii dense granule protein 25 (TgGRA25) interconnects parasite and host mitochondria in infected cells. Using a combination of biochemical and cell biologic approaches, we reveal that TgGRA25 contributes to mitochondrial-tethering by its association with the phosphatidic acid-producing mitochondrial phospholipase MitoPLD. TgGRA25/MitoPLD interactions suppress the efficiency of parasite egress from host cells. Moreover, targeted deletion of TgGRA25 in type II parasites caused dramatic deformation of the parasitophorous vacuole membrane and severe defects in the lytic cycle of T. gondii, indicating an essential role of TgGRA25 in parasite morphogenesis. Our results suggest the existence of multiple routes by which communication is maintained between the parasite and host mitochondria, and this translocation event could be a potential therapeutic target.