Characterization of two novel proteins involved in mitochondrial DNA anchoring in Trypanosoma brucei

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 mo...

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Bibliographic Details
Published in:PLoS pathogens 2023-07, Vol.19 (7), p.e1011486-e1011486
Main Authors: Amodeo, Simona, Bregy, Irina, Hoffmann, Anneliese, Fradera-Sola, Albert, Kern, Mara, Baudouin, Hélène, Zuber, Benoît, Butter, Falk, Ochsenreiter, Torsten
Format: Article
Language:English
Subjects:
Binding proteins
Biology and Life Sciences
Cell cycle
Circular DNA
Cytoplasm
Deoxyribonucleic acid
DNA
Genetic aspects
Genomes
Genomics
Identification and classification
Localization
Medicine and Health Sciences
Microscopy
Mitochondrial DNA
Parasites
Parasitological research
Phenotypes
Physiological aspects
Protein binding
Protein-protein interactions
Proteins
Proteomics
Protozoa
Quantitative analysis
Research and Analysis Methods
RNA-mediated interference
Structure
Trypanosoma brucei
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011486