Plasmodium falciparum has a limited repertoire of autophagy‐related genes (ATGs), and the functions of various proteins of the autophagy‐like pathway are not fully established in this protozoan parasite. Studies suggest that some of the autophagy proteins are crucial for parasite growth. PfATG18, for example, is essential for parasite replication and has a noncanonical role in apicoplast biogenesis. In this study, we demonstrate the conserved functions of PfATG18 in food vacuole (FV) dynamics and autophagy. Intriguingly, the P. falciparum FV is found to undergo fission and fusion and PfATG18 gets enriched at the interfaces of the newly generated multilobed FV during the process. In addition, expression of PfATG18 is induced upon starvation, both at the mRNA and protein level indicating its participation in the autophagy‐like pathway, which is independent of its role in apicoplast biogenesis. The study also shows that PfATG18 is transported to the FV via the haemoglobin trafficking pathway. Overall, this study establishes the conserved functions of Atg18 in this important apicomplexan.

The precise role of autophagy in P. falciparum remains largely unknown. Although a limited number of autophagy genes have been identified in this apicomplexan, only PfAtg8 has been characterized to a certain extent. On the basis of the expression levels of PfAtg8 and the putative PfAtg5, we report that the basal autophagy in this parasite is quite robust and mediates not only the intraerythrocytic development but also fresh invasion of red blood cells (RBCs) in the subsequent cycles. We demonstrate that the basal autophagy responds to both inducers and inhibitors of autophagy. In addition, the parasite survival upon starvation is temporally governed by the autophagy status. Brief periods of starvation, which induces autophagy, help survival while prolonged starvation decreases autophagy leading to stalled parasite growth and reduced invasion. Thus, starvation-induced autophagy is context dependent. Importantly, we report characterization of another autophagy marker in this parasite, the putative PfAtg5 (Pf3D7_1430400). PfAtg5 is expressed in all the intraerythrocytic stages and partially colocalizes with ER, mitochondria, apicoplast and PfAtg8. It is also present on the double membrane bound vesicles. Altogether, these studies pave way for the detailed dissection of P. falciparum autophagy machinery and insights into molecular and functional characterization of its players for developing new therapeutics as antimalarials.