Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance

Like any genome, mitochondrial DNA (mtDNA) also requires the action of topoisomerases to resolve topological problems in its maintenance, but for a long time, little was known about mitochondrial topoisomerases. The last years have brought a closer insight into the function of these fascinating enzy...

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Bibliographic Details
Published in:International journal of molecular sciences 2019-04, Vol.20 (8), p.2041
Main Authors: Goffart, Steffi, Hangas, Anu, Pohjoismäki, Jaakko L O
Format: Article
Language:English
Subjects:
Cell division
Concatamers
Deoxyribonucleic acid
DNA
DNA biosynthesis
Enzymes
Gene expression
Genomes
Homologous recombination
Homology
Mitochondrial DNA
mitochondrial DNA maintenance
mtDNA replication
Proteins
Replication
Review
Single-stranded DNA
topoisomerases
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Summary:Like any genome, mitochondrial DNA (mtDNA) also requires the action of topoisomerases to resolve topological problems in its maintenance, but for a long time, little was known about mitochondrial topoisomerases. The last years have brought a closer insight into the function of these fascinating enzymes in mtDNA topology regulation, replication, transcription, and segregation. Here, we summarize the current knowledge about mitochondrial topoisomerases, paying special attention to mammalian mitochondrial genome maintenance. We also discuss the open gaps in the existing knowledge of mtDNA topology control and the potential involvement of mitochondrial topoisomerases in human pathologies. While Top1mt, the only exclusively mitochondrial topoisomerase in mammals, has been studied intensively for nearly a decade, only recent studies have shed some light onto the mitochondrial function of Top2β and Top3α, enzymes that are shared between nucleus and mitochondria. Top3α mediates the segregation of freshly replicated mtDNA molecules, and its dysfunction leads to mtDNA aggregation and copy number depletion in patients. Top2β, in contrast, regulates mitochondrial DNA replication and transcription through the alteration of mtDNA topology, a fact that should be acknowledged due to the frequent use of Topoisomerase 2 inhibitors in medical therapy.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20082041