Das, S.

In Plasmodium falciparum, DNA replication and asynchronous nuclei formation precede cytokinesis during intraerythrocytic schizogony. Inhibition of fatty acids (FAs) import and impaired membrane biogenesis led to the arrest of mitosis through the inhibition of DNA replication and nuclei formation. On the iRBC surface, parasite ribosomal protein P2 (PfP2) complex mediated FAs import and membrane biogenesis, seemingly prior events before the commitment for DNA replication and nuclei formation. The inhibition of FAs import led to the degradation of histones by the evolutionarily conserved bacterial serine protease ClpP/ClpR in the parasite nucleus. Noncanonical arginine hyperphosphorylation by a novel arginine kinase in the nucleus was subjected for proteostasis and marks histones for degradation by ClpP/ClpR machinery. Inhibition of de novo FAs biosynthesis by an anti-cancer drug, Cerulenin and C75, in HEK293T and HCT116 carcinoma mammalian cells showed histone degradation. Lipid (L) induced histone proteostasis by ClpP/ClpR, seemingly an indispensable L-checkpoint before mitotic commitment.