A dynamin-like protein in Plasmodium falciparum plays an essential role in parasite growth, mitochondrial development and homeostasis during asexual blood stages

Abstract

Malaria parasites harbour a single mitochondrion, and its proper segregation during parasite multiplication is crucial for the propagation of the parasite within the host. Mitochondrial division machinery consists of several proteins that associate with the mitochondrial membrane during segregation. Here, we have identified a dynamin-like protein in P. falciparum, PfDyn2, and deciphered its role in mitochondrial growth and homeostasis. A GFP targeting approach combined with high-resolution microscopy studies showed that the PfDyn2 associates with the mitochondrial membrane at specific sites during mitochondrial division. The C-terminal degradation tag mediated inducible knock-down (iKD) of PfDyn2 significantly inhibited parasite growth. PfDyn2-iKD hindered mitochondrial development and functioning, decreased mtDNA replication, and induced mitochondrial oxidative stress, ultimately causing parasite death. Regulated overexpression of a phosphorylation mutant of PfDyn2 (Ser-612-Ala) did not affect the recruitment of PfDyn2 on the mitochondria; normal mitochondrial division and parasite growth showed that phosphorylation/dephosphorylation of this conserved serine residue (Ser612) may not be responsible for regulating recruitment of PfDyn2 to the mitochondrion. Overall, we show the essential role of PfDyn2 in mitochondrial development and maintaining its homeostasis during the asexual cycle of the parasite.