Apicoplast lipoic acid protein ligase B is not essential for Plasmodium falciparum.
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.
Günther
Svenja
S
Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Wallace
Lynsey
L
Patzewitz
Eva-Maria
EM
McMillan
Paul J
PJ
Storm
Janet
J
Wrenger
Carsten
C
Bissett
Ryan
R
Smith
Terry K
TK
Müller
Sylke
S
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
D016054:DNA, Protozoan; D008074:Lipoproteins; D015800:Protozoan Proteins; D008063:Thioctic Acid; D010453:Peptide Synthases; C072322:lipoate-protein ligase