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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...

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Autores principales: Goffart, Steffi, Hangas, Anu, Pohjoismäki, Jaakko L. O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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