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Article
Subject Categories: Cellular Metabolism | Microbiology & Pathogens
The EMBO Journal (2006) 25, 3214–3222, doi:10.1038/sj.emboj.7601189
Published online 15 June 2006
Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplast
Michael J Crawford1, Nadine Thomsen-Zieger2, Manisha Ray1, Joachim Schachtner3, David S Roos1 and Frank Seeber2
1 Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
2 FB Biologie, Parasitologie, Philipps Universität, Marburg, Germany
3 FB Biologie, Physiologie, Philipps Universität, Marburg, Germany

To whom correspondence should be addressed
Frank Seeber, FB Biologie, Parasitologie, Universität Marburg, Karl-von-Frisch-Str., 35043 Marburg, Germany. Tel.: +49 6421 2823498; Fax: +49 6421 2821531; E-mail: seeber@staff.uni-marburg.de

Received 10 January 2006; Accepted 17 May 2006; Published online 15 June 2006.
Abstract
In contrast to other eukaryotes, which manufacture lipoic acid, an essential cofactor for several vital dehydrogenase complexes, within the mitochondrion, we show that the plastid (apicoplast) of the obligate intracellular protozoan parasite Toxoplasma gondii is the only site of de novo lipoate synthesis. However, antibodies specific for protein-attached lipoate reveal the presence of lipoylated proteins in both, the apicoplast and the mitochondrion of T. gondii. Cultivation of T. gondii-infected cells in lipoate-deficient medium results in substantially reduced lipoylation of mitochondrial (but not apicoplast) proteins. Addition of exogenous lipoate to the medium can rescue this effect, showing that the parasite scavenges this cofactor from the host. Exposure of T. gondii to lipoate analogues in lipoate-deficient medium leads to growth inhibition, suggesting that T. gondii might be auxotrophic for this cofactor. Phylogenetic analyses reveal the secondary loss of the mitochondrial lipoate synthase gene after the acquisition of the plastid. Our studies thus reveal an unexpected metabolic deficiency in T. gondii and raise the question whether the close interaction of host mitochondria with the parasitophorous vacuole is connected to lipoate supply by the host.
Keywords: apicomplexa, apicoplast, lipoic acid, metabolism, Toxoplasma gondii
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