PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum

Anat Florentin, David W. Cobb, Jillian D. Fishburn, Michael J. Cipriano, Paul S. Kim, Manuel A. Fierro, Boris Striepen, Vasant Muralidharan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The deadly malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid, known as the apicoplast, that functions to produce essential metabolites, and drugs that target the apicoplast are clinically effective. Several prokaryotic caseinolytic protease (Clp) genes have been identified in the Plasmodium genome. Using phylogenetic analysis, we focused on the Clp members that may form a regulated proteolytic complex in the apicoplast. We genetically targeted members of this complex and generated conditional mutants of the apicoplast-localized PfClpC chaperone and PfClpP protease. Conditional inhibition of the PfClpC chaperone resulted in growth arrest and apicoplast loss and was rescued by addition of the essential apicoplast-derived metabolite IPP. Using a double-conditional mutant parasite line, we discovered that the chaperone activity is required to stabilize the mature protease, revealing functional interactions. These data demonstrate the essential function of PfClpC in maintaining apicoplast integrity and its role in regulating the proteolytic activity of the Clp complex. Plasmodium falciparum contains a unique organelle, the apicoplast. Using genetic and phenotypic assays, Florentin et al. characterize the apicoplast Clp chaperone and protease. They find that the chaperone is essential for protease stability and that together they function to maintain organelle integrity and segregation into daughter cells.

Original languageAmerican English
Pages (from-to)1746-1756
Number of pages11
JournalCell Reports
Volume21
Issue number7
DOIs
StatePublished - 14 Nov 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Author(s)

Keywords

  • Clp
  • IPP
  • Plasmodium
  • apicoplast
  • caseinolytic protease
  • chaperone
  • malaria

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