title: Apicoplast lipoic acid protein ligase B is not essential for Plasmodium falciparum.
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.
authors: Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors: Svenja
authors: S
authors: Günther
authors: Lynsey
authors: L
authors: Wallace
authors: Eva-Maria
authors: EM
authors: Patzewitz
authors: Paul J
authors: PJ
authors: McMillan
authors: Janet
authors: J
authors: Storm
authors: Carsten
authors: C
authors: Wrenger
authors: Ryan
authors: R
authors: Bissett
authors: Terry K
authors: TK
authors: Smith
authors: Sylke
authors: S
authors: Müller
mesh_terms: D000818:Animals; D016054:DNA, Protozoan / Q000235:genetics; D008401:Gas Chromatography-Mass Spectrometry; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017125:Genes, Protozoan / Q000235:genetics; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015388:Organelles / Q000201:enzymology*; D010453:Peptide Synthases / Q000502:physiology*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D015800:Protozoan Proteins / Q000502:physiology*; D008063:Thioctic Acid / Q000378:metabolism*; D053058:Trophozoites / Q000254:growth & development / Q000378:metabolism
chemical_list: D016054:DNA, Protozoan; D008074:Lipoproteins; D015800:Protozoan Proteins; D008063:Thioctic Acid; D010453:Peptide Synthases; C072322:lipoate-protein ligase