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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514783/ https://www.ncbi.nlm.nih.gov/pubmed/31027213 http://dx.doi.org/10.3390/ijms20082041 |
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author | Goffart, Steffi Hangas, Anu Pohjoismäki, Jaakko L. O. |
author_facet | Goffart, Steffi Hangas, Anu Pohjoismäki, Jaakko L. O. |
author_sort | Goffart, Steffi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6514783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65147832019-05-30 Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance Goffart, Steffi Hangas, Anu Pohjoismäki, Jaakko L. O. Int J Mol Sci Review 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. MDPI 2019-04-25 /pmc/articles/PMC6514783/ /pubmed/31027213 http://dx.doi.org/10.3390/ijms20082041 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Goffart, Steffi Hangas, Anu Pohjoismäki, Jaakko L. O. Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance |
title | Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance |
title_full | Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance |
title_fullStr | Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance |
title_full_unstemmed | Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance |
title_short | Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance |
title_sort | twist and turn—topoisomerase functions in mitochondrial dna maintenance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514783/ https://www.ncbi.nlm.nih.gov/pubmed/31027213 http://dx.doi.org/10.3390/ijms20082041 |
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