Premium
The human malaria parasite Plasmodium falciparum has distinct organelle‐specific lipoylation pathways
Author(s) -
Wrenger Carsten,
Müller Sylke
Publication year - 2004
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2004.04112.x
Subject(s) - lipoic acid , biology , plasmodium falciparum , apicoplast , biochemistry , dna ligase , transferase , biosynthesis , enzyme , gene , plastid , malaria , chloroplast , immunology , antioxidant
Summary Lipoic acid is an essential cofactor of α‐keto acid dehydrogenase complexes (KADHCs). This study shows that Plasmodium falciparum possesses two distinct lipoylation pathways that are found in separate subcellular localizations. Lipoic acid synthesis comprising lipoic acid synthase and lipoyl‐ACP:protein N ‐lipoyl transferase is present in the parasite's apicoplast, whereas the second pathway consisting of lipoic acid protein ligase is located in the parasite's mitochondrion. The two localizations were established by overexpressing green fluorescent protein fusions of the N‐terminal sequences of lipoic acid synthase and lipoic acid protein ligase in intraerythrocytic stages of P. falciparum . Northern and Western blot analyses revealed that the genes/proteins encoding lipoic acid synthase, lipoyl‐ACP:protein N ‐lipoyl transferase and lipoic acid protein ligase are expressed maximally in the early and late stages of P. falciparum erythrocytic development. The functionality of the three proteins was proven by complementation of bacteria deficient in lipA and lipB . Our results show that P. falciparum possesses two independent pathways, with different locations, responsible for the post‐translational modification of KADHCs. Both pathways fundamentally differ from those in the human host. As KADHCs provide metabolites that are required for essential biosynthetic processes such as fatty acid biosynthesis and haem biosynthesis, the two lipoylation pathways of P. falciparum might be attractive therapeutic targets against malaria.