p166 links membrane and intramitochondrial modules of the trypanosomal tripartite attachment complex

PLoS Pathog. 2022 Jun 16;18(6):e1010207. doi: 10.1371/journal.ppat.1010207. eCollection 2022 Jun.


The protist parasite Trypanosoma brucei has a single mitochondrion with a single unit genome termed kinetoplast DNA (kDNA). Faithfull segregation of replicated kDNA is ensured by a complicated structure termed tripartite attachment complex (TAC). The TAC physically links the basal body of the flagellum with the kDNA spanning the two mitochondrial membranes. Here, we characterized p166 as the only known TAC subunit that is anchored in the inner membrane. Its C-terminal transmembrane domain separates the protein into a large N-terminal region that interacts with the kDNA-localized TAC102 and a 34 aa C-tail that binds to the intermembrane space-exposed loop of the integral outer membrane protein TAC60. Whereas the outer membrane region requires four essential subunits for proper TAC function, the inner membrane integral p166, via its interaction with TAC60 and TAC102, would theoretically suffice to bridge the distance between the OM and the kDNA. Surprisingly, non-functional p166 lacking the C-terminal 34 aa still localizes to the TAC region. This suggests the existence of additional TAC-associated proteins which loosely bind to non-functional p166 lacking the C-terminal 34 aa and keep it at the TAC. However, binding of full length p166 to these TAC-associated proteins alone would not be sufficient to withstand the mechanical load imposed by the segregating basal bodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Kinetoplast / genetics
  • DNA, Kinetoplast / metabolism
  • Flagella / metabolism
  • Genome, Mitochondrial*
  • Mitochondrial Membranes / metabolism
  • Protozoan Proteins / metabolism
  • Trypanosoma brucei brucei* / genetics
  • Trypanosoma brucei brucei* / metabolism


  • DNA, Kinetoplast
  • Protozoan Proteins

Grants and funding

This work was supported by the following grants: NCCR RNA & Disease, a National Centre of Competence in Research, supported by the Swiss National Science Foundation, grant number 182880, to AS Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, grant number 175563, to AS Deutsche Forschungsgemeinschaft, grant number 390939984, to FNV SFB1381, grant number 403222702, to FNV Emmy-Noether Programm, to FNV Deutsche Forschungsgemeinschaft, grant number, 403222702/SFB 1381, to BW The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.