Feeling hot in here: thermotolerance and drug sensitivity in malaria parasites

During its complex life cycle, the malaria parasite survives dramatic changes in environmental temperature. Protein prenylation is required during asexual replication of Plasmodium falciparum, and heat shock protein 40 is post-translationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation of Hsp40 orthologs controls its localization and function, including temperature stress survival. We find that plastidial isopentenyl pyrophosphate (IPP) synthesis and protein farnesylation are required for malaria parasite survival after cold and heat shock. Furthermore, loss of HSP40 farnesylation alters its membrane attachment and interaction with proteins involved in crucial biological processes, such as glycolysis and cytoskeletal organization. Together, this work reveals that farnesylation of HSP40 in P. falciparum is a novel essential function of plastidial isoprenoid biosynthesis and may be a key antiparasitic target for treatment of symptomatic febrile malaria episodes.