Biogenesis of the mitochondrial DNA inheritance machinery in the mitochondrial outer membrane of Trypanosoma brucei

PLoS Pathog. 2017 Dec 29;13(12):e1006808. doi: 10.1371/journal.ppat.1006808. eCollection 2017 Dec.


Mitochondria cannot form de novo but require mechanisms that mediate their inheritance to daughter cells. The parasitic protozoan Trypanosoma brucei has a single mitochondrion with a single-unit genome that is physically connected across the two mitochondrial membranes with the basal body of the flagellum. This connection, termed the tripartite attachment complex (TAC), is essential for the segregation of the replicated mitochondrial genomes prior to cytokinesis. Here we identify a protein complex consisting of three integral mitochondrial outer membrane proteins-TAC60, TAC42 and TAC40-which are essential subunits of the TAC. TAC60 contains separable mitochondrial import and TAC-sorting signals and its biogenesis depends on the main outer membrane protein translocase. TAC40 is a member of the mitochondrial porin family, whereas TAC42 represents a novel class of mitochondrial outer membrane β-barrel proteins. Consequently TAC40 and TAC42 contain C-terminal β-signals. Thus in trypanosomes the highly conserved β-barrel protein assembly machinery plays a major role in the biogenesis of its unique mitochondrial genome segregation system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Kinetoplast / biosynthesis*
  • DNA, Kinetoplast / genetics*
  • DNA, Mitochondrial / biosynthesis*
  • DNA, Mitochondrial / genetics*
  • Genome, Mitochondrial
  • Genome, Protozoan
  • Humans
  • Mitochondrial Dynamics
  • Mitochondrial Membranes / metabolism
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Protein Sorting Signals / genetics
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Trypanosoma brucei brucei / genetics*
  • Trypanosoma brucei brucei / metabolism*
  • Trypanosoma brucei brucei / pathogenicity


  • DNA, Kinetoplast
  • DNA, Mitochondrial
  • Multiprotein Complexes
  • Protein Sorting Signals
  • Protozoan Proteins

Grants and funding

Research in the groups of BW and CM was funded by the Deutsche Forschungsgemeinschaft and the Excellence Initiative of the German Federal & State Governments (EXC 294 BIOSS Centre for Biological Signalling Studies) and the RTG2202. Research in the lab of AS was supported by grant 138355 and in part by the NCCR "RNA & Disease" both funded by the Swiss National Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.