Apicoplast lipoic acid protein ligase B is not essential for Plasmodium falciparum

Svenja Guenther, Lynsey Wallace, Eva-Maria Patzewitz, Paul J. McMillan, Janet Storm, Carsten Wrenger, Ryan Bissett, Terry K Smith, Sylke Mueller

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)
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Abstract

Lipoic acid (LA) is an essential cofactor of alpha-keto acid dehydrogenase complexes (KADHs) and the glycine cleavage system. In Plasmodium, LA is attached to the KADHs by organelle-specific lipoylation pathways. Biosynthesis of LA exclusively occurs in the apicoplast, comprising octanoyl-[acyl carrier protein]: protein N-octanoyltransferase (LipB) and LA synthase. Salvage of LA is mitochondrial and scavenged LA is ligated to the KADHs by LA protein ligase 1 (LplA1). Both pathways are entirely independent, suggesting that both are likely to be essential for parasite survival. However, disruption of the LipB gene did not negatively affect parasite growth despite a drastic loss of LA (> 90%). Surprisingly, the sole, apicoplast-located pyruvate dehydrogenase still showed lipoylation, suggesting that an alternative lipoylation pathway exists in this organelle. We provide evidence that this residual lipoylation is attributable to the dual targeted, functional lipoate protein ligase 2 (LplA2). Localisation studies show that LplA2 is present in both mitochondrion and apicoplast suggesting redundancy between the lipoic acid protein ligases in the erythrocytic stages of P. falciparum.

Original languageEnglish
Article numbere189
Pages (from-to)1938-1949
Number of pages12
JournalPLoS Pathogens
Volume3
Issue number12
DOIs
Publication statusPublished - Dec 2007

Keywords

  • ESCHERICHIA-COLI
  • APICOMPLEXAN PARASITES
  • LIPOYLATION PATHWAYS
  • ARABIDOPSIS-THALIANA
  • TOXOPLASMA-GONDII
  • MALARIA PARASITES
  • CRYSTAL-STRUCTURE
  • BOVINE LIVER
  • LIPB GENES
  • LIPOATE

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