Calcium transfer from the ER to other organelles for optimal signaling in <i>Toxoplasma gondii</i>.

Abstract

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