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Peer-reviewedCC BY 4.0PLOS Biology

The kinetoplastid-specific transcription factor mtTF1 is essential for mitochondrial gene expression and maxicircle replication in Trypanosoma brucei

  • Bianca Manuela Berger1
  • Enrico Santini2
  • Himaja Manjunatha3
  • Lea Trost4
  • Markus Gerber
  • Hauke S. Hillen
  • Torsten Ochsenreiter
4 affiliations
  1. 1Institute of Cell Biology, University of Bern, Bern, Switzerland
  2. 2Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
  3. 3Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany
  4. 4Research Group Structure and Function of Molecular Machines, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
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Abstract

Mitochondrial DNA replication and gene expression are essential for cell survival. In Trypanosoma brucei, a protozoan animal and human parasite, the mitochondrial RNA polymerase (mtRNAP, Tb927.11.5780) plays roles in both transcription and DNA replication. This study identifies and characterizes the first mitochondrial transcription factor (mtTF1, Tb927.6.4510) in the Kinetoplastea. The mtRNAP and mtTF1 form a high-molecular-weight complex that localizes to the kinetoplast DNA (kDNA) and is essential for parasite survival in both life cycle stages. Their localization is interdependent, and both proteins influence maxicircle replication, but not minicircle replication. Knockdown of either protein results in altered gene expression, particularly affecting the minor strand of the mitochondrial genome. mTF1 specifically binds to kDNA and since it is unique to the Kinetoplastea, it might prove to be a promising drug target.

How mitochondrial transcription and DNA replication are coordinated in Trypanosoma brucei remains unclear. This study identifies mtTF1, the first mitochondrial transcription factor in Kinetoplastea required for gene expression and maxicircle replication.

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Cite

BibTeXRIS
BibTeX
@article{berger2026kinetoplastidspecific,
  title = {{The kinetoplastid-specific transcription factor mtTF1 is essential for mitochondrial gene expression and maxicircle replication in Trypanosoma brucei}},
  author = {Bianca Manuela Berger and Enrico Santini and Himaja Manjunatha and Lea Trost and Markus Gerber and Hauke S. Hillen and Torsten Ochsenreiter},
  journal = {PLOS Biology},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pbio.3003945},
  url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003945},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The kinetoplastid-specific transcription factor mtTF1 is essential for mitochondrial gene expression and maxicircle replication in Trypanosoma brucei
AU  - Bianca Manuela Berger
AU  - Enrico Santini
AU  - Himaja Manjunatha
AU  - Lea Trost
AU  - Markus Gerber
AU  - Hauke S. Hillen
AU  - Torsten Ochsenreiter
PY  - 2026
DA  - 2026/09/21
JO  - PLOS Biology
DO  - 10.1371/journal.pbio.3003945
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003945
AB  - Mitochondrial DNA replication and gene expression are essential for cell survival. In Trypanosoma brucei, a protozoan animal and human parasite, the mitochondrial RNA polymerase (mtRNAP, Tb927.11.5780) plays roles in both transcription and DNA replication. This study identifies and characterizes the first mitochondrial transcription factor (mtTF1, Tb927.6.4510) in the Kinetoplastea. The mtRNAP and mtTF1 form a high-molecular-weight complex that localizes to the kinetoplast DNA (kDNA) and is essential for parasite survival in both life cycle stages. Their localization is interdependent, and both proteins influence maxicircle replication, but not minicircle replication. Knockdown of either protein results in altered gene expression, particularly affecting the minor strand of the mitochondrial genome. mTF1 specifically binds to kDNA and since it is unique to the Kinetoplastea, it might prove to be a promising drug target.  How mitochondrial transcription and DNA replication are coordinated in Trypanosoma brucei remains unclear. This study identifies mtTF1, the first mitochondrial transcription factor in Kinetoplastea required for gene expression and maxicircle replication.
SN  - 1545-7885
ER  -