TY - JOUR TI - The NTP generating activity of pyruvate kinase II is critical for apicoplast maintenance in Plasmodium falciparum AU - Swift, Russell P AU - Rajaram, Krithika AU - Keutcha, Cyrianne AU - Liu, Hans B AU - Kwan, Bobby AU - Dziedzic, Amanda AU - Jedlicka, Anne E AU - Prigge, Sean T A2 - Soldati-Favre, Dominique A2 - Ferguson, Neil M VL - 9 PY - 2020 DA - 2020/08/20 SP - e50807 C1 - eLife 2020;9:e50807 DO - 10.7554/eLife.50807 UR - https://doi.org/10.7554/eLife.50807 AB - The apicoplast of Plasmodium falciparum parasites is believed to rely on the import of three-carbon phosphate compounds for use in organelle anabolic pathways, in addition to the generation of energy and reducing power within the organelle. We generated a series of genetic deletions in an apicoplast metabolic bypass line to determine which genes involved in apicoplast carbon metabolism are required for blood-stage parasite survival and organelle maintenance. We found that pyruvate kinase II (PyrKII) is essential for organelle maintenance, but that production of pyruvate by PyrKII is not responsible for this phenomenon. Enzymatic characterization of PyrKII revealed activity against all NDPs and dNDPs tested, suggesting that it may be capable of generating a broad range of nucleotide triphosphates. Conditional mislocalization of PyrKII resulted in decreased transcript levels within the apicoplast that preceded organelle disruption, suggesting that PyrKII is required for organelle maintenance due to its role in nucleotide triphosphate generation. KW - apicoplast KW - malaria KW - Pyruvate Kinase KW - plasmodium KW - microarray KW - carbon metabolism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -