Nutrient Sensing and Growth Control in Plasmodium: Beyond mTOR Signaling.

The mechanistic target of rapamycin (mTOR) signaling pathway is a central regulator of nutrient sensing, metabolism, growth, and stress adaptation in most eukaryotes. Malaria parasites of the genus Plasmodium, however, lack identifiable orthologues of mTOR kinase and its associated signaling complexes, raising the question of how these organisms coordinate environmental sensing with developmental progression and proliferation. Here, we discuss emerging evidence suggesting that Plasmodium has evolutionarily replaced the canonical mTOR signaling axis with a distributed regulatory architecture composed of parasite-specific nutrient sensors, kinase-based signaling pathways, translational repression mechanisms, and unconventional autophagy processes. Components such as KIN, PI3K, eIF2α kinases, eIF4E-interacting protein DOZI, and Maf1 collectively preserve many hallmark outputs of mTOR signaling, including metabolic adaptation, stress tolerance, developmental plasticity, and reversible quiescence. In addition, malaria parasites interact with host mTOR pathways during infection, potentially exploiting host-derived anabolic signaling environments to support intracellular development. These findings suggest that Plasmodium exemplifies an extreme case of signaling plasticity in eukaryotic evolution, demonstrating how essential mTOR-associated functions can be maintained despite the apparent loss of the pathway itself.