Apicoplast Lipoic Acid Protein Ligase B Is Not Essential for Plasmodium falciparum

PLoS Pathogens

Sylke Müller¹  Ryan Bissett¹  Eva-Maria Patzewitz¹  Svenja Günther¹  Janet Storm¹  Carsten Wrenger²  Terry K Smith²  Lynsey Wallace²  Paul J McMillan² 

[1] Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom;Wellcome Centre for Parasitology, Glasgow, United Kingdom

关键词: Plasmodium;    Lipoylation;    Parasitic cell cycles;    Cellular structures;    organelles;    Fatty acids;    Biosynthesis;    Parasitic life cycles;    Lipoic acids;   

DOI  :  10.1371/journal.ppat.0030189

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY