| Mitochondrial lipoic acid scavenging is essential for Plasmodium berghei liver stage development. | |
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MedLine Citation:
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PMID: 22128915 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Lipoic acid is an essential cofactor for enzymes that participate in key metabolic pathways in most organisms. While in mammalian cells lipoylated proteins reside exclusively in the mitochondria, apicomplexan parasites of the genus Plasmodium harbor two independent lipoylation pathways in the mitochondrion and the apicoplast, a second organelle of endosymbiotic origin. Protein lipoylation in the apicoplast relies on de novo lipoic acid synthesis while lipoylation of proteins in the mitochondrion depends on scavenging of lipoic acid from the host cell. Here, we analyze the impact of lipoic acid scavenging on the development of Plasmodium berghei liver stage parasites. Treatment of P. berghei-infected HepG2 cells with the lipoic acid analog 8-bromo-octanoic acid (8-BOA) abolished lipoylation of mitochondrial enzyme complexes in the parasite while lipoylation of apicoplast proteins was not affected. Parasite growth as well as the ability of the parasites to successfully complete liver stage development by merosome formation were severely impaired but not completely blocked by 8-BOA. Liver stage parasites were most sensitive to 8-BOA treatment during schizogony, the phase of development when the parasite grows and undergoes extensive nuclear division to form a multinucleated syncytium. Live cell imaging as well as immunofluorescence analysis and electronmicroscopy studies revealed a close association of both host cell and parasite mitochondria with the parasitophorous vacuole membrane suggesting that host cell mitochondria might be involved in lipoic acid uptake by the parasite from the host cell. |
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Authors:
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Christina Deschermeier; Leonie-Sophie Hecht; Frauke Bach; Katharina Rützel; Rebecca R Stanway; Andreas Nagel; Frank Seeber; Volker T Heussler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-30 |
Journal Detail:
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Title: Cellular microbiology Volume: - ISSN: 1462-5822 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883691 Medline TA: Cell Microbiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 Blackwell Publishing Ltd. |
Affiliation:
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Bernhard Nocht Institute for Tropical Medicine, Department of Molecular Parasitology, Malaria Laboratory I, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany University of Bern, Institute of Cell Biology, Baltzerstraße 4, 3012 Bern, Switzerland Robert Koch Institute, Department of Parasitology, Nordufer 20, 13353 Berlin, Germany. |
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