The parasite Trypanosoma brucei lives and replicates in insect vectors like the fly. During the mating process, both its nucleus and mitochondrion replicate and exchange their genetic information, while the mitochondrial mechanism is still incompletely understood. The review “Mitochondrial genome maintenance—the kinetoplast story” in FEMS Microbiology Reviews discusses what is currently known about the molecular components and mechanisms of mitochondrial genome replication in trypanosomes. Simona Amodeo and Irina Bregy explain for the #FEMSmicroBlog what we can learn about mitochondrial inheritance from this parasite. #FascinatingMicrobes
Trypanosoma brucei and its mitochondrion
The replication of mitochondrial DNA is an essential process in most eukaryotes. Just as the genome size and the organization of mitochondrial DNA – the so-called kinetoplast – can be highly diverse, its replication process also shows considerable diversity.
Trypanosoma brucei is the causative agent of sleeping sickness and occurs exclusively in sub-Saharan Africa. The protozoan parasite is transmitted by the tse tse fly in which it lives entirely extracellularly, in the blood or interstitial spaces in tissues.
T. brucei contains quite an astounding mitochondrion together with its genome. In contrast to most other cells, Trypanosomes only contain one mitochondrial organelle with a single mitochondrial genome.
During the mating process in the fly vector, Trypanosomes exchange DNA not only between their nuclear genomes but also between their mitochondrial genomes. The review “Mitochondrial genome maintenance—the kinetoplast story” in FEMS Microbiology Reviews summarizes the current knowledge of all factors involved in the replication of the mitochondrial genome in Trypanosomes. The article further provides a conceptual model for the unusual inheritance pattern observed in the mitochondrial genome of the parasite.
How Trypanosomes maintain their mitochondrial genome
The structure of the mitochondrial genome is of spectacular complexity. Transmission electron microscopy revealed a disc-like electron-dense shape of the kinetoplast. It consists of thousands of circular DNA molecules that are categorized into two major groups: maxicircles and minicircles.
A mitochondrion contains about 25 copies of the larger maxicircle per cell about 23 kDa in size. These encode the mitochondrial genes – also called cryptogenes.
Many cryptogenes require posttranscriptional modifications by adding and depleting uridine residues. Only after this RNA-editing process do the transcripts contain the appropriate information to translate into the correct proteins.
Throughout the RNA editing process, the cell uses small guide RNAs to define the positions of insertion and deletion. The guide RNAs are encoded on the second type of the mitochondrial DNA molecule: the minicircles.
A Trypanosome cell generally contains about 5000 minicircle copies each about 1 kb in size. Each of these DNA molecules is physically interlocked with at least three other minicircle molecules. And into this chainmail network of minicircles, the maxicircles are further interwoven.
The complexity of this structure raises questions about how Trypanosome cells organize the replication and segregation of the kinetoplast DNA. In particular, it is still mysterious how this process is coordinated during the exchange of genetic material throughout the mating process.
The review provides a possible framework for the replication and segregation of mitochondrial minicircles based on the available current knowledge. This model would also explain the genomic diversity observed in trypanosome mitochondria and the mechanism for maintenance.
- Read the review “Mitochondrial genome maintenance—the kinetoplast story” by Amodeo et al. (2022).
About the authors of this blog
Irina Bregy is currently pursuing her PhD in molecular and structural biology at the University of Bern. Embedded in the research groups of Torsten Ochsenreiter and Benoît Zuber, she is working on an interdisciplinary project that combines Trypanosome mitochondrial biology with modern structural biology. She discovered her passion for Trypanosomes back in her Bachelor’s degree when she first joined Torsten Ochsenreiter’s research group for a short practical. She then returned to the group and successfully completed a Master’s degree in molecular biology.
Simona Amodeo is the mother of a one-year-old son and is currently a postdoctoral researcher in the lab of Professor André Schneider at the Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, where she investigates unique aspects of cytosolic ribosome biogenesis in T. brucei. The review had its beginning with the writing of her PhD thesis during her time as a PhD student in the lab of Professor Torsten Ochsenreiter at the Institute of Cell Biology, University of Bern. In her PhD project, she investigated mitochondrial DNA replication and segregation in T. brucei.
Torsten Ochsenreiter is a Professor of Cell and Microbiology at the University of Bern in Switzerland. His lab is interested in mitochondrial biogenesis using the eukaryotic model system of Trypanosoma brucei to especially understand mitochondrial genome replication and segregation.
About this blog section
The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.
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