Calcium transfer from the ER to other organelles for optimal signaling in Toxoplasma gondii

Ca 2+ signaling in cells begins with the opening of Ca 2+ channels in either the plasma membrane (PM) or endoplasmic reticulum (ER), leading to a sharp increase in the physiologically low (<100 nM) cytosolic Ca 2+ level. The temporal and spatial regulation of Ca² + is crucial for the precise activation of key biological processes. In the apicomplexan parasite Toxoplasma gondii , which infects approximately one-third of the global population, Ca² + signaling governs essential aspects of the parasite’s infection cycle. T. gondii relies on Ca² + signals to regulate pathogenic traits, with several Ca² + -signaling components playing critical roles. Ca 2+ entry from the extracellular environment has been demonstrated in T. gondii for both, extracellular parasites, exposed to high Ca 2+ , and intracellular parasites, which acquire Ca² + from host cells during host Ca² + signaling events. Active egress, an essential step of the parasite’s infection cycle, is preceded by a large increase in cytosolic Ca 2+ , most likely initiated by release from intracellular stores. However, extracellular Ca 2+ is also necessary to reach a cytosolic Ca 2+ threshold required for timely egress. In this study, we investigated the mechanism of intracellular Ca² + store replenishment and identified a central role for the SERCA-Ca 2+ -ATPase in maintaining Ca² + homeostasis within the ER and in other organelles. We demonstrate mitochondrial Ca 2+ uptake, which occurs by transfer of Ca 2+ from the ER, likely through membrane contact sites. Our findings suggest that the T. gondii ER plays a key role in sequestering and redistributing Ca² + to intracellular organelles following Ca² + influx at the PM.