Skip to main contentSkip to search and navigation

UEF eREPOSITORY

    • English
    • suomi
  • English 
    • English
    • suomi
  • Login
View Item 
  •   Home
  • Artikkelit
  • Luonnontieteiden ja metsätieteiden tiedekunta
  • View Item
  •   Home
  • Artikkelit
  • Luonnontieteiden ja metsätieteiden tiedekunta
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2

Thumbnail
Files
Article (2.742Mb)
Self archived version
published version
Date
2018
Author(s)
Hangas, Anu
Aasumets, Koit
Kekäläinen, Nina J
Paloheinä, Mika
Pohjoismäki, Jaakko L
Gerhold, Joachim M
Goffart, Steffi
Unique identifier
10.1093/nar/gky793
Metadata
Show full item record
More information
Research Database SoleCris

Self-archived article

Citation
Hangas, Anu. Aasumets, Koit. Kekäläinen, Nina J. Paloheinä, Mika. Pohjoismäki, Jaakko L. Gerhold, Joachim M. Goffart, Steffi. (2018). Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2.  NUCLEIC ACIDS RESEARCH, [Published: 31 August 2018], 10.1093/nar/gky793.
Rights
© Authors
Licensed under
CC BY-NC http://creativecommons.org/licenses/by-nc/4.0/
Abstract

Maintenance of topological homeostasis is vital for gene expression and genome replication in all organisms. Similar to other circular genomes, also mitochondrial DNA (mtDNA) is known to exist in various different topological forms, although their functional significance remains unknown. We report here that both known type II topoisomerases Top2α and Top2β are present in mammalian mitochondria, with especially Top2β regulating the supercoiling state of mtDNA. Loss of Top2β or its inhibition by ciprofloxacin results in accumulation of positively supercoiled mtDNA, followed by cessation of mitochondrial transcription and replication initiation, causing depletion of mtDNA copy number. These mitochondrial effects block both cell proliferation and differentiation, possibly explaining some of the side effects associated with fluoroquinolone antibiotics. Our results show for the first time the importance of topology for maintenance of mtDNA homeostasis and provide novel insight into the mitochondrial effects of fluoroquinolones.

URI
https://erepo.uef.fi/handle/123456789/6970
Link to the original item
http://dx.doi.org/10.1093/nar/gky793
Publisher
Oxford University Press (OUP)
Collections
  • Luonnontieteiden ja metsätieteiden tiedekunta [1109]
University of Eastern Finland
OpenAccess
eRepo
erepo@uef.fi
OpenUEF
Service provided by
the University of Eastern Finland Library
Library web pages
Twitter
Facebook
Youtube
Library blog
 sitemap
Search

Browse

All of the ArchiveResource types & CollectionsBy Issue DateAuthorsTitlesSubjectsFacultyDepartmentFull organizationSeriesMain subjectThis CollectionBy Issue DateAuthorsTitlesSubjectsFacultyDepartmentFull organizationSeriesMain subject

My Account

Login
University of Eastern Finland
OpenAccess
eRepo
erepo@uef.fi
OpenUEF
Service provided by
the University of Eastern Finland Library
Library web pages
Twitter
Facebook
Youtube
Library blog
 sitemap