Basal and starvation-induced autophagy mediates parasite survival during intraerythrocytic stages of Plasmodium falciparum .

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 Pf Atg8 has been characterized to a certain extent. On the basis of the expression levels of Pf Atg8 and the putative Pf Atg5, 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 Pf Atg5 ( Pf 3D7_1430400). PfAtg 5 is expressed in all the intraerythrocytic stages and partially colocalizes with ER, mitochondria, apicoplast and Pf Atg8. 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.