Amodeo, Simona; Bregy, Irina; Hoffmann, Anneliese; Fradera-Sola, Albert; Kern, Mara; Baudouin, Hélène; Zuber, Benoît; Butter, Falk; Ochsenreiter, Torsten (2023). Characterization of two novel proteins involved in mitochondrial DNA anchoring in Trypanosoma brucei. PLoS pathogens, 19(7), e1011486. Public Library of Science 10.1371/journal.ppat.1011486
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Trypanosoma brucei is a single celled eukaryotic parasite in the group of the Kinetoplastea. The parasite harbors a single mitochondrion with a singular mitochondrial genome that is known as the kinetoplast DNA (kDNA). The kDNA consists of a unique network of thousands of interlocked circular DNA molecules. To ensure proper inheritance of the kDNA to the daughter cells, the genome is physically linked to the basal body, the master organizer of the cell cycle in trypanosomes. The connection that spans, cytoplasm, mitochondrial membranes and the mitochondrial matrix is mediated by the Tripartite Attachment Complex (TAC). Using a combination of proteomics and RNAi we test the current model of hierarchical TAC assembly and identify TbmtHMG44 and TbKAP68 as novel candidates of a complex that connects the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 each leads to a strong kDNA loss but not missegregation phenotype as previously defined for TAC components. We demonstrate that the proteins rely on both the TAC and the kDNA for stable localization to the interface between these two structures. In vitro experiments suggest a direct interaction between TbmtHMG44 and TbKAP68 and that recombinant TbKAP68 is a DNA binding protein. We thus propose that TbmtHMG44 and TbKAP68 are part of a distinct complex connecting the kDNA to the TAC.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
09 Interdisciplinary Units > Microscopy Imaging Center (MIC) 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 08 Faculty of Science > Department of Biology > Institute of Cell Biology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Amodeo, Simona, Bregy, Irina, Hoffmann, Anneliese, Kern, Mara Deborah, Baudouin, Hélène Clémentine Margareta, Zuber, Benoît, Ochsenreiter, Torsten |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1553-7366 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
18 Jul 2023 07:36 |
Last Modified: |
14 Dec 2023 20:43 |
Publisher DOI: |
10.1371/journal.ppat.1011486 |
PubMed ID: |
37459364 |
BORIS DOI: |
10.48350/184903 |
URI: |
https://boris.unibe.ch/id/eprint/184903 |
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