The NTP generating activity of pyruvate kinase ii is critical for apicoplast maintenance in plasmodium falciparum

Russell P. Swift, Krithika Rajaram, Cyrianne Keutcha, Hans B. Liu, Bobby Kwan, Amanda Dziedzic, Anne E. Jedlicka, Sean T. Prigge

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere50807
Pages (from-to)1-45
Number of pages45
JournaleLife
Volume9
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'The NTP generating activity of pyruvate kinase ii is critical for apicoplast maintenance in plasmodium falciparum'. Together they form a unique fingerprint.

Cite this