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

Günther, S., Wallace, L., Patzewitz, E.-M., McMillan, P.J., Storm, J., Wrenger, C., Bissett, R., Smith, T.K. and Muller, S. (2007) Apicoplast lipoic acid protein ligase B is not essential for Plasmodium falciparum. PLoS Pathogens, 3(12), e189. (doi: 10.1371/journal.ppat.0030189)

Abstract

Lipoic acid (LA) is an essential cofactor of α-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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muller, Professor Sylke and Patzewitz, Ms Eva-Maria and Storm, Dr Janet and Wallace, Dr Lynsey
• Authors: Günther, S., Wallace, L., Patzewitz, E.-M., McMillan, P.J., Storm, J., Wrenger, C., Bissett, R., Smith, T.K., and Muller, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 07 December 2007
• Copyright Holders: Copyright © 2007 Gunther et al.
• First Published: First published PLoS Pathogens 3(12):e189
• Publisher Policy: Reproduced under Creative Commons License