title: Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance.
abstract: Mitochondria cannot form de novo but require mechanisms allowing their inheritance to daughter cells. In contrast to most other eukaryotes Trypanosoma brucei has a single mitochondrion whose single-unit genome is physically connected to the flagellum. Here we identify a β-barrel mitochondrial outer membrane protein, termed tripartite attachment complex 40 (TAC40), that localizes to this connection. TAC40 is essential for mitochondrial DNA inheritance and belongs to the mitochondrial porin protein family. However, it is not specifically related to any of the three subclasses of mitochondrial porins represented by the metabolite transporter voltage-dependent anion channel (VDAC), the protein translocator of the outer membrane 40 (TOM40), or the fungi-specific MDM10, a component of the endoplasmic reticulum-mitochondria encounter structure (ERMES). MDM10 and TAC40 mediate cellular architecture and participate in transmembrane complexes that are essential for mitochondrial DNA inheritance. In yeast MDM10, in the context of the ERMES, is postulated to connect the mitochondrial genomes to actin filaments, whereas in trypanosomes TAC40 mediates the linkage of the mitochondrial DNA to the basal body of the flagellum. However, TAC40 does not colocalize with trypanosomal orthologs of ERMES components and, unlike MDM10, it regulates neither mitochondrial morphology nor the assembly of the protein translocase. TAC40 therefore defines a novel subclass of mitochondrial porins that is distinct from VDAC, TOM40, and MDM10. However, whereas the architecture of the TAC40-containing complex in trypanosomes and the MDM10-containing ERMES in yeast is very different, both are organized around a β-barrel protein of the mitochondrial porin family that mediates a DNA-cytoskeleton linkage that is essential for mitochondrial DNA inheritance.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Felix
authors.initials: F
authors.lastname: Schnarwiler
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Moritz
authors.initials: M
authors.lastname: Niemann
authors.affiliation: Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Doiron
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Anke
authors.initials: A
authors.lastname: Harsman
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Sandro
authors.initials: S
authors.lastname: Käser
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Jan
authors.initials: J
authors.lastname: Mani
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Astrid
authors.initials: A
authors.lastname: Chanfon
authors.affiliation: Institute of Immunology and Infection Research and Centre for Immunity, Infection, and Evolution, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom;
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Dewar
authors.affiliation: Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany;
authors.forename: Silke
authors.initials: S
authors.lastname: Oeljeklaus
authors.affiliation: Division of Human Genetics, Department of Paediatrics and Clinical Research, Inselspital, University of Bern, CH-3010 Bern, Switzerland;
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Jackson
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Mascha
authors.initials: M
authors.lastname: Pusnik
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung and BIOSS Centre for Biological Signalling Studies, Universität Freiburg, D-79104 Freiburg, Germany; and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmidt
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung and BIOSS Centre for Biological Signalling Studies, Universität Freiburg, D-79104 Freiburg, Germany; and.
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0002-6709-4684
authors.initials: S
authors.lastname: Hiller
authors.affiliation: Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany;
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.affiliation: Institute of Immunology and Infection Research and Centre for Immunity, Infection, and Evolution, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom;
authors.forename: Achim C
authors.initials: AC
authors.lastname: Schnaufer
authors.affiliation: Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland;
authors.forename: Torsten
authors.initials: T
authors.lastname: Ochsenreiter
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland; andre.schneider@dcb.unibe.ch.
authors.forename: André
authors.initials: A
authors.lastname: Schneider
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D016000:Cluster Analysis; D003599:Cytoskeleton / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D050259:Genes, Mitochondrial / Q000235:genetics*; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D010802:Phylogeny; D018272:Porins / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014346:Trypanosoma brucei brucei / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D018272:Porins; D015800:Protozoan Proteins
keywords: organelle; parasitic protozoa