Evidence map›Paper›PMID 30169847›Full record

ArticleNucleic acids research2018

Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2.

Anu Hangas, Koit Aasumets, Nina J Kekäläinen, Mika Paloheinä, Jaakko L Pohjoismäki, Joachim M Gerhold, Steffi Goffart

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 147 citations in OpenAlex.

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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Anu HangasDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Koit AasumetsInstitute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
Nina J KekäläinenDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Mika PaloheinäDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Jaakko L PohjoismäkiDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Joachim M GerholdInstitute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
Steffi GoffartDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
University of Eastern Finland · FIUniversity of Tartu · EE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Cell LineCiprofloxacinDNA, MitochondrialDNA ReplicationDNA Topoisomerases, Type IIHumansMitochondriaPoly-ADP-Ribose Binding ProteinsTranscription, GeneticCiprofloxacinDNA, MitochondrialDNA Topoisomerases, Type IIPoly-ADP-Ribose Binding ProteinsTOP2A protein, humanTOP2B protein, human

Identifiers

PMID30169847
PMCPMC6182158
OpenAlexW2888825853

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.