title: Legionella pneumophila secretes a mitochondrial carrier protein during infection.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Dolezal
authors.forename: Margareta
authors.initials: M
authors.lastname: Aili
authors.forename: Janette
authors.initials: J
authors.lastname: Tong
authors.forename: Jhih-Hang
authors.initials: JH
authors.lastname: Jiang
authors.forename: Carlo M T
authors.initials: CM
authors.lastname: Marobbio
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Marobbio
authors.forename: Sau Fung
authors.initials: SF
authors.lastname: Lee
authors.forename: Ralf
authors.initials: R
authors.lastname: Schuelein
authors.forename: Simon
authors.initials: S
authors.lastname: Belluzzo
authors.forename: Eva
authors.initials: E
authors.lastname: Binova
authors.forename: Aurelie
authors.initials: A
authors.lastname: Mousnier
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.forename: Giulia
authors.initials: G
authors.lastname: Giannuzzi
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Palmieri
authors.forename: Kipros
authors.initials: K
authors.lastname: Gabriel
authors.forename: Thomas
authors.initials: T
authors.lastname: Naderer
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hartland
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
mesh_terms: D000255:Adenosine Triphosphate; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D041101:Neorickettsia sennetsu / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D002352:Carrier Proteins; D008565:Membrane Proteins; D000255:Adenosine Triphosphate