Legionella pneumophila secretes a mitochondrial carrier protein during infection

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

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43 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)e1002459
JournalPLoS Pathogens
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Adenosine Triphosphate
  • Bacterial Proteins
  • Bacterial Secretion Systems
  • Carrier Proteins
  • Genetic Complementation Test
  • HeLa Cells
  • Humans
  • Legionella pneumophila
  • Legionnaires' Disease
  • Membrane Proteins
  • Neorickettsia sennetsu
  • Saccharomyces cerevisiae

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  • Cite this

    Dolezal, P., Aili, M., Tong, J., Jiang, J-H., Marobbio, C. M. T., Marobbio, C. M., Lee, S. F., Schuelein, R., Belluzzo, S., Binova, E., Mousnier, A., Frankel, G., Giannuzzi, G., Palmieri, F., Gabriel, K., Naderer, T., Hartland, E. L., & Lithgow, T. (2012). Legionella pneumophila secretes a mitochondrial carrier protein during infection. PLoS Pathogens, 8(1), e1002459. https://doi.org/10.1371/journal.ppat.1002459