Legionella pneumophila secretes a mitochondrial carrier protein during infection

Pavel Dolezal, Margareta Aili, Janette Tong, Jhih-Hang Jiang, Carlo MT Marobbio, Sau Fung Lee, Ralf Schuelein, Simon Belluzzo, Eva Binova, Aurelie Mousnier, Gad M Frankel, Giulia Giannuzzi, Ferdinando Palmieri, Kipros Gabriel, Thomas Naderer, Elizabeth L Hartland, Trevor J Lithgow

Research output: Contribution to journalArticleResearchpeer-review

50 Citations (Scopus)

Abstract

The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionellanucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire s disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms.
Original languageEnglish
Pages (from-to)1 - 13
Number of pages13
JournalPLoS Pathogens
Volume8
Issue number1 (Art. ID: e1002459)
DOIs
Publication statusPublished - 2012

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